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1.
Arq. bras. cardiol ; 112(1): 3-10, Jan. 2019. graf
Article in English | LILACS | ID: biblio-973840

ABSTRACT

Abstract Background: Vein graft restenosis has an adverse impact on bridge vessel circulation and patient prognosis after coronary artery bypass grafting. Objectives: We used the extravascular supporter α-cyanoacrylate (α-CA), the local application rapamycin/sirolimus (RPM), and a combination of the two (α-CA-RPM) in rat models of autogenous vein graft to stimulate vein graft change. The aim of our study was to observe the effect of α-CA, RPM, and α-CA-RPM on vein hyperplasia. Methods: Fifty healthy Sprague Dawley (SD) rats were randomized into the following 5 groups: sham, control, α-CA, RPM, and α-CA-RPM. Operating procedure as subsequently described was used to build models of grafted rat jugular vein on carotid artery on one side. The level of endothelin-1 (ET-1) was determined by enzyme-linked immunosorbent assay (ELISA). Grafted veins were observed via naked eye 4 weeks later; fresh veins were observed via microscope and image-processing software in hematoxylin-eosin (HE) staining and immunohistochemistry after having been fixed and stored" (i.e. First they were fixed and stored, and second they were observed); α-Smooth Muscle Actin (αSMA) and von Willebrand factor (vWF) were measured with reverse transcription-polymerase chain reaction (RT-PCR). Comparisons were made with single-factor analysis of variance and Fisher's least significant difference test, with p < 0.05 considered significant. Results: We found that intimal thickness of the α-CA, RPM, and α-CA-RPM groups was lower than that of the control group (p < 0.01), and the thickness of the α-CA-RPM group was notably lower than that of the α-CA and RPM groups (p < 0.05). Conclusion: RPM combined with α-CA contributes to inhibiting intimal hyperplasia in rat models and is more effective for vascular patency than individual use of either α-CA or RPM.


Resumo Fundamento: Reestenose de enxertos venosos tem um impacto adverso na circulação de pontagens e no prognóstico de pacientes após a cirurgia de revascularização miocárdica. Objetivos: Nós utilizamos α-cianoacrilato (α-CA) como suporte extravascular, rapamicina/sirolimus (RPM) como aplicação local e a combinação dos dois (α-CA-RPM) em modelos de enxerto venoso autógeno em ratos para estimular mudança no enxerto venoso. O objetivo do nosso estudo foi observar o efeito de α-CA, RPM e α-CA-RPM na hiperplasia venosa. Métodos: Cinquenta ratos Sprague Dawley (SD) saudáveis foram randomizados nos 5 grupos seguintes: sham, controle, α-CA, RPM e α-CA-RPM. O procedimento operacional descrito subsequentemente foi utilizado para construir modelos de enxertos da veia jugular na artéria carótida em ratos, em um lado. O nível de endotelina-1 (ET-1) foi determinado por ensaio de imunoabsorção enzimática (ELISA). As veias enxertadas foram observadas a olho nu 4 semanas após; as veias frescas foram observadas via microscópio e software de processamento de imagem com coloração hematoxilina-eosina (HE) e imuno-histoquímica depois de serem fixadas e armazenadas; α-actina do músculo liso (αSMA) e o fator de von Willebrand (vWF) foram medidos com reação em cadeia da polimerase-transcriptase reversa (RT-PCR). Realizaram-se as comparações com análise de variância de fator único (ANOVA) e o teste de diferença mínima significativa (LSD) de Fisher, com p < 0,05 sendo considerado estatisticamente significante. Resultados: Nós achamos que a espessura intimal nos grupos α-CA, RPM e α-CA-RPM era menor que no grupo controle (p < 0,01) e a espessura no grupo α-CA-RPM era notavelmente menor que nos grupos α-CA e RPM (p < 0,05). Conclusão: A combinação de RPM e α-CA contribui à inibição de hiperplasia em modelos em ratos e é mais efetivo para patência vascular que uso individual de α-CA ou RPM.


Subject(s)
Animals , Male , Female , Tunica Intima/drug effects , Tunica Intima/pathology , Sirolimus/pharmacology , Cyanoacrylates/pharmacology , Hyperplasia/prevention & control , Time Factors , Enzyme-Linked Immunosorbent Assay , Carotid Arteries/pathology , Carotid Arteries/transplantation , Random Allocation , Coronary Artery Bypass/adverse effects , Reproducibility of Results , Actins/analysis , Treatment Outcome , Rats, Sprague-Dawley , Endothelin-1/blood , Reverse Transcriptase Polymerase Chain Reaction , Cell Proliferation/drug effects , Disease Models, Animal , Drug Combinations , Graft Occlusion, Vascular/etiology , Graft Occlusion, Vascular/pathology , Graft Occlusion, Vascular/prevention & control , Jugular Veins/pathology , Jugular Veins/transplantation
3.
Rev. nefrol. diál. traspl ; 39(1): 26-37, ene. 2019. tab
Article in English | LILACS | ID: biblio-1007060

ABSTRACT

INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in chronic renal failure. It's known that vascular calcification (VC) and carotid intima media thickness (CIMT) are strongly associated with cardiovascular diseases. Growth arrest specific protein 6 (Gas6) is a vitamin K-dependent protein and regulates various processes such as proliferation, cell survival, migration and inflammation. Gas6 is known to protect endothelial cells and vascular smooth muscle cells against apoptosis by inhibiting Bcl-2 induced Caspase 3 activation. The relationship between Gas6 and cardiovascular diseases has been demonstrated in many mouse models and cell cultures. However, there are conflicting reports whether Gas6 levels are increasing or decreasing in human studies of diabetic and/or chronic renal failure. In present study the aim was to examine plasma Gas6 levels and its relation with CIMT and coronary artery calcification score (CACS) in chronic kidney disease (CKD) patients. METHODS: Total of 137 patients of which 32 chronic hemodialysis and 105 predialysis patients as well as 73 healthy controls were enrolled in the study. Human Gas6 levels in serum samples were studied by ELISA method. CIMT was measured by ultrasonography. CACS was measured by multislice computed tomography. RESULTS: The mean age was 54.37±16.61 years in dialysis group, 55.20±14.80 years in predialysis group and 53.26±9.04 years in control group. Serum creatinine was 0.78±0.16 mg/dl in the control group and 1.96±1.64 mg/dl in the predialysis group and 5.94±1.55 mg/dl in the dialysis group. 24 hours urine protein levels were significally higher in the dialysis group than the predialysis and the control group. CIMT values were similar in predialysis and dialysis groups. These values were significantly higher than the control group. Although CACS was higher in dialysis group than predialysis and control group, the results were not statistically significant since the distribution range was very wide. Gas6 was 98.84±53.32 ng/mL in the control group and statistically higher than the dialysis (63.85±38.92 ng/mL) and the predialysis groups (54.96±38.49 ng/mL) (p=0.001). Gas6 levels were lower in diabetic patients than non-diabetics (53.69±35.26 ng/mL, 69.26±47.50 ng/mL, p=0.023, respectively). Negative correlation was detected between Gas6 and age, BMI, CACS, carotid IMT and proteinuria. In the logistic regression analysis, Gas6 remained significantly associated with BMI, CIMT and proteinuria. CONCLUSION: In our study, a negative correlation of Gas6 with BMI, CACS, CIMT and proteinuria and lower Gas6 levels in diabetic patients support that decreased Gas6 levels in chronic renal failure may have a role in vascular calcification through altered glucose tolerance, chronic inflammation, endothelial dysfunction and increased apoptosis. Our study has an importance because it is the first study showing a relation between Gas6 and proteinuria, CACS and carotid IMT in patients with chronic renal failure


INTRODUCCIÓN: La enfermedad cardiovascular es la principal causa de mortalidad y morbilidad en la insuficiencia renal crónica. Se sabe que la calcificación vascular (CV) y el grosor de la íntima-media de la carótida (CIMT, por sus siglas en inglés) están vinculados de forma muy estrecha con enfermedades cardiovasculares. La proteína específica del gen 6 de la detención de crecimiento (Gas6) es una proteína dependiente de la vitamina K y regula diversos procesos, como la proliferación, la supervivencia celular, la migración y la inflamación. La proteína Gas6 es conocida por proteger las células endoteliales y las células musculares lisas vasculares contra la apoptosis mediante la inhibición de la activación de la caspasa-3 inducida por la proteína Bcl-2. Se ha demostrado la relación entre la Gas6 y las enfermedades cardiovasculares en muchos modelos de ratones y cultivos celulares. Sin embargo, existen informes contradictorios acerca de si los niveles de Gas6 aumentan o disminuyen en estudios de humanos con insuficiencia renal crónica y/o diabética. En este estudio, el objetivo fue examinar los niveles plasmáticos de Gas6 y su relación con el CIMT y la puntuación de calcificación de las arterias coronarias (CACS, por sus siglas en inglés) en pacientes con enfermedad renal crónica (ERC). MATERIAL Y MÉTODOS: Un total de 137 pacientes fueron incluidos en el estudio, de los cuales 32 estaban en hemodiálisis crónica, 105 en prediálisis, y 73 pacientes representaban controles sanos. Se esudiaron los niveles de Gas6 en muestras de suero mediante el método ELISA. El CIMT se midió por medio de ecografía. La CACS se midió mediante tomografía computarizada multicorte. RESULTADOS: La edad media fue de 54,37 ± 16,61 años en el grupo de diálisis; 55,20 ± 14,80 años en el grupo de prediálisis, y 53,26 ± 9,04 años en el grupo de control. La creatinina sérica fue de 0,78 ± 0,16 mg/dl en el grupo de control; 1,96 ± 1,64 mg/dl en el de prediálisis, y 5,94 ± 1,55 mg/dl en el de diálisis. Las concentraciones de proteína en orina de 24 horas fueron significativamente más altas en el grupo de diálisis que en los de prediálisis y control. Los valores del CIMT fueron similares en los grupos de prediálisis y de diálisis. Estos valores fueron considerablemnete más altos que en el grupo de control. Aunque la CACS fue más alta en el grupo de diálisis que en los otros dos, los resultados no fueron estadísticamente significativos, ya que el rango de distribución fue muy amplio. La proteína Gas6 fue de 98,84 ± 53,32 ng/ml en el grupo de control y estadísticamente más alta que en los grupos de diálisis (63,85 ± 38,92 ng/ml) y de prediálisis (54,96 ± 38,49 ng/ml) (p = 0,001). Los niveles de Gas6 fueron más bajos en los pacientes diabéticos que en los no diabéticos (53,69 ± 35,26 ng/ml; 69,26 ± 47,50 ng/ml, [p = 0,023], respectivamente). Se detectó una correlación negativa entre la proteína Gas6 y la edad, el IMC, la CACS, el CIMT y la proteinuria. En el análisis de regresión logística, la Gas6 se mantuvo estrechamente relacionada con el IMC, el CIMT y la proteinuria. CONCLUSIÓN: En nuestro estudio, la correlación negativa de Gas6 con IMC, CACS, CIMT y proteinuria, y los niveles más bajos de Gas6 en pacientes diabéticos sustentan la idea de que la disminución de los niveles de Gas6 en la insuficiencia renal crónica puede jugar un papel en la calcificación vascular a través de la tolerancia alterada a la glucosa, la inflamación crónica, la disfunción endotelial y el aumento de la apoptosis. La importancia de nuestro estudio radica en que es el primero que muestra una relación entre la Gas6 y la proteinuria, la CACS y el CIMT en pacientes con insuficiencia renal crónica


Subject(s)
Humans , Vascular Diseases/complications , Calcinosis , Tunica Intima/abnormalities , Coronary Vessel Anomalies , Fibroblast Growth Factor 6/blood
4.
Article in English | WPRIM | ID: wpr-763019

ABSTRACT

Atherosclerosis is a widespread and chronic progressive arterial disease that has been regarded as one of the major causes of death worldwide. It is caused by the deposition of cholesterol, fats, and other substances in the tunica intima which leads to narrowing of the blood vessels, loss of elasticity, and arterial wall thickening, thus causing difficulty in blood flow. Natural products have been used as one of the most important strategies for the treatment and prevention of cardiovascular diseases for a long time. In recent decades, as interests in natural products including medicinal herbs have increased, many studies regarding natural compounds that are effective against atherosclerosis have been conducted. The purpose of this review is to provide a brief over-view of the natural compounds that have been used for the treatment and prevention of atherosclerosis, and their mechanisms of action based on recent research.


Subject(s)
Atherosclerosis , Biological Products , Blood Vessels , Cardiovascular Diseases , Cause of Death , Cholesterol , Classification , Elasticity , Fats , Plants, Medicinal , Tunica Intima
5.
Arq. bras. cardiol ; 111(4): 562-568, Oct. 2018. tab, graf
Article in English | LILACS | ID: biblio-973770

ABSTRACT

Abstract Background: Restenosis after percutaneous coronary intervention in coronary heart disease remains an unsolved problem. Clusterin (CLU) (or Apolipoprotein [Apo] J) levels have been reported to be elevated during the progression of postangioplasty restenosis and atherosclerosis. However, its role in neointimal hyperplasia is still controversial. Objective: To elucidate the role Apo J in neointimal hyperplasia in a rat carotid artery model in vivo with or without rosuvastatin administration. Methods: Male Wistar rats were randomly divided into three groups: the control group (n = 20), the model group (n = 20) and the statin intervention group (n = 32). The rats in the intervention group were given 10mg /kg dose of rosuvastatin. A 2F Fogarty catheter was introduced to induce vascular injury. Neointima formation was analyzed 1, 2, 3 and 4 weeks after balloon injury. The level of Apo J was measured by real-time PCR, immunohistochemistry and western blotting. Results: Intimal/medial area ratio (intimal/medial, I/M) was increased after balloon-injury and reached the maximum value at 4weeks in the model group; I/M was slightly increased at 2 weeks and stopped increasing after rosuvastatin administration. The mRNA and protein levels of Apo J in carotid arteries were significantly upregulated after rosuvastatin administration as compared with the model group, and reached maximum values at 2 weeks, which was earlier than in the model group (3 weeks). Conclusion: Apo J served as an acute phase reactant after balloon injury in rat carotid arteries. Rosuvastatin may reduce the neointima formation through up-regulation of Apo J. Our results suggest that Apo J exerts a protective role in the restenosis after balloon-injury in rats.


Resumo Fundamento: A reestenose após intervenção coronária percutânea (ICP) após doença coronariana continua um problema não solucionado. Estudos relataram que os níveis de clusterina (CLU), também chamada de apolipoproteína (Apo) J, encontram-se elevados na progressão da reestenose pós-angioplastia e na aterosclerose. Contudo, seu papel na hihperplasia neointimal ainda é controverso. Objetivo: Elucidar o papel da Apo J na hiperplasia neointimal na artéria carótida utilizando um modelo experimental com ratos in vivo, com e sem intervenção com rosuvastatina. Métodos: ratos Wistar machos foram divididos aleatoriamente em três grupos - grupo controle (n = 20), grupo modelo (n = 20), e grupo intervenção com estatina (n = 32). Os ratos no grupo intervenção receberam 10 mg/kg de rosuvastatina. Um cateter Fogarty 2 F foi introduzido para induzir lesão vascular. A formação de neoíntima foi analisada 1, 2, 3 e 4 semanas após lesão com balão. Concentrações de Apo J foram medidas por PCR em tempo real, imuno-histoquímica e western blotting. Resultados: A razão área íntima/média (I/M) aumentou após a lesão com balão e atingiu o valor máximo 4 semanas pós-lesão no grupo modelo; observou-se um pequeno aumento na I/M na semana 2, que cessou após a administração de rosuvastatina. Os níveis de mRNA e proteína da Apo J nas artérias carótidas aumentaram significativamente após administração de rosuvastatina em comparação ao grupo modelo, atingindo o máximo na semana 2, mais cedo em comparação ao grupo modelo (semana 3). Conclusão: A Apo J atuou como reagente de fase aguda após lesão com balão nas artérias carótidas de ratos. A rosuvastatina pode reduzir a formação de neoíntoma por aumento de Apo J. Nossos resultados sugerem que a Apo J exerce um papel protetor na reestenose após lesão com balão em ratos.


Subject(s)
Animals , Male , Angioplasty, Balloon, Coronary/adverse effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Carotid Artery Injuries/drug therapy , Coronary Restenosis/drug therapy , Clusterin/drug effects , Anticholesteremic Agents/pharmacology , Time Factors , Enzyme-Linked Immunosorbent Assay , Immunohistochemistry , Carotid Arteries/drug effects , Carotid Arteries/pathology , Random Allocation , Blotting, Western , Reproducibility of Results , Treatment Outcome , Tunica Media/drug effects , Tunica Media/pathology , Tunica Intima/drug effects , Tunica Intima/pathology , Rats, Wistar , Protective Agents/pharmacology , Carotid Artery Injuries/etiology , Carotid Artery Injuries/pathology , Coronary Restenosis/etiology , Coronary Restenosis/pathology , Clusterin/analysis , Real-Time Polymerase Chain Reaction , Rosuvastatin Calcium/pharmacology
6.
Article in English | WPRIM | ID: wpr-691364

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model.</p><p><b>METHODS</b>The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut (25, 50 and 75 mg/kg) with 10 rats of each group. The rats were treated with or without Rut (25, 50, 75 mg/kg) by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen (PCNA) and smooth muscle (SM) α-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 (ERK2), MAPK phosphatase-1 (MKP-1) and endothelial nitric oxide synthase (eNOS) were determined by real-time reverse transcription-polymerase chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 (p-ERK2) were examined by Western blotting. The plasma contents of nitric oxide (NO) and cyclic guanosine 3',5'-monophosphate (cGMP) were also determined.</p><p><b>RESULTS</b>Compared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury (P<0.05 or P<0.01). The positive expression rate of PCNA was decreased, while the expression rate of SM α-actin obviously increased in the vascular wall after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01). Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated (P<0.05 or P<0.01). The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downregulated after Rut (50 and 75 mg/kg) administration (P<0.05 or P<0.01), respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma (P<0.05 or P<0.01).</p><p><b>CONCLUSION</b>Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.</p>


Subject(s)
Actins , Metabolism , Animals , Carotid Arteries , Metabolism , Pathology , Carotid Artery Injuries , Drug Therapy , Genetics , Pathology , Cyclic GMP , Blood , Disease Models, Animal , Gene Expression Regulation , Hyperplasia , Indole Alkaloids , Pharmacology , Therapeutic Uses , Male , Nitric Oxide , Blood , Phosphorylation , Proliferating Cell Nuclear Antigen , Metabolism , Quinazolines , Pharmacology , Therapeutic Uses , RNA, Messenger , Genetics , Metabolism , Rats, Sprague-Dawley , Tunica Intima , Pathology
7.
Article in English | WPRIM | ID: wpr-740667

ABSTRACT

Fibromuscular dysplasia (FMD) of the coronary artery is a rare cause of sudden cardiac death; however, its prevalence and fatality may have been overlooked so far. A 47-year-old man complained of pain in his back and shoulder and became unconscious. Despite resuscitation, he died 3 hours after symptom onset. The heart weight was in the normal range; however, all three major coronary arteries showed intimal thickening without atherosclerosis or inflammatory cell infiltration. Fragmentations and duplications of the internal elastic lamina which are histologic features of intimal fibroplasia, a focal-type FMD, were observed. The prevalence of coronary FMD remains unknown, although it may be related to spontaneous coronary artery dissection and sudden death. The histopathologic confirmation of coronary FMD and exclusion of other possible coronary diseases through autopsy are essential to reveal the nature of the disease and therefore apply the information in dealing with legal problems after death.


Subject(s)
Atherosclerosis , Autopsy , Cause of Death , Coronary Disease , Coronary Vessels , Death, Sudden , Death, Sudden, Cardiac , Fibromuscular Dysplasia , Heart , Humans , Middle Aged , Prevalence , Reference Values , Resuscitation , Shoulder , Tunica Intima
8.
Chinese Medical Journal ; (24): 1113-1121, 2017.
Article in English | WPRIM | ID: wpr-266854

ABSTRACT

<p><b>OBJECTIVE</b>Vascular calcification is the consequence of the complex interaction between genetic, environmental, and vascular factors, which ultimately lead to the deposition of calcium in the tunica intima (atherosclerotic calcification) or tunica media (Mönckenberg's sclerosis). Vascular calcification is also closely related to other pathologies, such as diabetes mellitus, dyslipidemia, and chronic kidney disease. It has been concluded that the degree of vascular calcification may vary from person to person, even if the associated pathologies and environmental factors are the same. Therefore, this suggests an important genetic contribution to the development of vascular calcification. This review aimed to find the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways.</p><p><b>DATA SOURCES</b>We conducted an exhaustive search in Scopus, EBSCO, and PubMed with the keywords "genetics and vascular calcification", "molecular pathways, genetic and vascular calcification" and included the main articles from January 1995 up to August 2016. We focused on the most recent evidence about vascular calcification pathophysiology regarding the genetic aspects and molecular pathways.</p><p><b>STUDY SELECTION</b>The most valuable published original and review articles related to our objective were selected.</p><p><b>RESULTS</b>Vascular calcification is a multifactorial disease; thus, its pathophysiology cannot be explained by a single specific factor, rather than by the result of the association of several genetic variants, molecular pathway interactions, and environmental factors that promote its development.</p><p><b>CONCLUSION</b>Although several molecular aspects of this mechanism have been elucidated, there is still a need for a better understanding of the factors that predispose to this disease.</p>


Subject(s)
Diabetes Mellitus , Metabolism , Dyslipidemias , Metabolism , Humans , Kidney Failure, Chronic , Metabolism , Renal Insufficiency, Chronic , Metabolism , Tunica Intima , Metabolism , Tunica Media , Metabolism , Vascular Calcification , Metabolism
9.
Chinese Medical Journal ; (24): 1327-1332, 2017.
Article in English | WPRIM | ID: wpr-330621

ABSTRACT

<p><b>BACKGROUND</b>The autologous saphenous vein is the most common conduit for coronary artery bypass grafting, but the vein graft disease will occur. This study used Matrigel basement membrane matrix with many different growth factors to promote vasa vasorum neovascularization and extenuate the hypoxia to improve remodeling.</p><p><b>METHODS</b>This study observed the hypoxia and thickness of the vein grafts at different times. Normal veins and vein grafts with 15 min of ischemia one day postoperatively were harvested in the neck of rabbits. Paired vein grafts with 15 min ischemia bilaterally (control vs. Matrigel basement membrane matrix) were performed and harvested at 2, 6, and 12 weeks postoperatively. The rabbits were randomly divided into four postoperative groups (six rabbits in each group): Group 1, one day postoperatively; Group 2, 2 weeks postoperatively; Group 3, 6 weeks postoperatively; and Group 4, 12 weeks postoperatively. The dimensions of vessel wall were captured, and the mean thicknesses of intima, media, and adventitia were measured. The hypoxia-inducible factor (HIF)-1α and HIF-2α labeling indices of intima, media, and adventitia were also measured.</p><p><b>RESULTS</b>In Group 1, the labeling index of HIF-1α was high in the normal vein and decreased significantly in the vein graft one day postoperatively (intima: 80 ± 3% vs. 12 ± 1%, P = 0.01; media: 67 ± 5% vs. 11 ± 1%, P = 0.01; adventitia: 40 ± 10% vs. 7 ± 2%, P = 0.03). The labeling index of HIF-2α had similar trend as HIF-1α (intima: 80 ± 10% vs. 10 ± 5%, P = 0.02; media: 60 ± 14% vs. 12 ± 2%, P = 0.01; adventitia: 45 ± 20% vs. 10 ± 4%, P = 0.03). Compared with the control vein grafts, vein grafts with Matrigel basement membrane matrix had lower labeling indices of HIF-1α and HIF-2α in media and adventitia at Group 2 (HIF-1α: 34 ± 5% vs. 20 ± 4%, P = 0.04 for media; 23 ± 3% vs. 11 ± 2%, P = 0.03 for adventitia; HIF-2α: 37 ± 6% vs. 21 ± 4%, P = 0.03 for media; 24 ± 4% vs. 13 ± 2%, P = 0.04 for adventitia) and Group 3 (HIF-1α: 33 ± 4% vs. 7 ± 2%, P = 0.04 for media; 13 ± 3% vs. 3 ± 1%, P = 0.02 for adventitia; HIF-2α: 27 ± 4% vs. 12 ± 3%, P = 0.02 for media; 19 ± 2% vs. 6 ± 1%, P = 0.02 for adventitia). There were no differences in mean thickness of intima, media, and adventitia between bilateral vein grafts at 2, 6, and 12 weeks postoperatively.</p><p><b>CONCLUSIONS</b>This study indicated that promoting vasa vasorum neovascularization of vein grafts extenuated hypoxia, but did not influence the intimal hyperplasia of the wall.</p>


Subject(s)
Animals , Basic Helix-Loop-Helix Transcription Factors , Metabolism , Hyperplasia , Pathology , Hypoxia-Inducible Factor 1 , Metabolism , Hypoxia-Inducible Factor 1, alpha Subunit , Metabolism , Neovascularization, Pathologic , Pathology , Postoperative Period , Rabbits , Saphenous Vein , Pathology , Tunica Intima , Pathology , Vasa Vasorum , Pathology
10.
Article in English | WPRIM | ID: wpr-812096

ABSTRACT

The aims of the present study were to determine the effects of heparin-derived oligosaccharides (HDOs) on vascular intimal hyperplasia (IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of action. An animal model was established by rubbing the endothelia within the common carotid artery (CCA) in male rabbits. The rabbits were fed a high-cholesterol diet. Arterial IH was determined by histopathological changes to the CCA. Serum lipids were detected using an automated biochemical analysis. Expressions of mRNAs for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), scavenger receptor class B type I (SR-BI), and ATP-binding cassette transporter A1 (ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were analyzed by Western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and bFGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the mRNA and protein expression levels of VEGF, bFGF, VCAM-1, MCP-1, and SR-BI in the arterial wall; however, ABCA-1 expression level was elevated. HDO treatment led to a reduction in serum lipids (total cholesterol, triglycerides, high-density and low-density lipoproteins). Our results from the rabbit model indicated that HDOs could ameliorate IH and underlying mechanism might involve VEGF, bFGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.


Subject(s)
ATP Binding Cassette Transporter 1 , Animals , Carotid Artery Injuries , Drug Therapy , Pathology , Chemokine CCL2 , Heparin , Therapeutic Uses , Hyperplasia , Male , Oligosaccharides , Therapeutic Uses , Rabbits , Tunica Intima , Pathology , Vascular Cell Adhesion Molecule-1 , Vascular Endothelial Growth Factor A
11.
Rev. bras. cir. cardiovasc ; 31(4): 291-299, July-Sept. 2016. tab, graf
Article in English | LILACS | ID: biblio-829740

ABSTRACT

Abstract Objective: Intimal hyperplasia is associated with graft failure and vascular sutures in the first year after surgery and in postangioplasty restenosis. Allium sativum (common garlic) lowers cholesterol and has antioxidant effects; it also has antiplatelet and antitumor properties and, therefore, has great potential to reduce or inhibit intimal hyperplasia of the arteries. Our objective is to determine if the garlic has an efficacy to inhibit myointimal hyperplasia compared to cilostazol. Methods: Female New Zealand rabbits were divided into the following groups (n=10 each) according to treatment: group A, garlic, 800 µg×kg-1×day-1, orally; group C, cilostazol, 50 mg.day-1, orally; group PS, 10 ml of 0.9% physiological saline solution, orally. Our primary is the difference of the mean of myointimal hyperplasia. Statistical analysis was performed by using ANOVA and Tukey tests, as well as the Chi-square test. We calculated the 95% confidence interval for each point estimate, and the P value was set as < 0.05. Results: Group PS had a mean hyperplasia rate of 35.74% (95% CI, 31.76–39.71%); group C, 16.21% (95% CI, 13.36–19.05%); and group A, 21.12% (95% CI, 17.26–25.01%); P<0.0001. Conclusion: We conclude that Allium sativum had the same efficacy in inhibiting myointimal hyperplasia when compared to the positive control, cilostazol.


Subject(s)
Animals , Female , Rabbits , Arteriosclerosis/prevention & control , Tetrazoles/pharmacology , Tunica Intima/pathology , Garlic/chemistry , Arteriosclerosis/pathology , Immunohistochemistry , Platelet Aggregation Inhibitors , Cilostazol , Hyperplasia/prevention & control
12.
Rev. Col. Bras. Cir ; 43(1): 28-34, Jan.-Feb. 2016. tab, graf
Article in English | LILACS | ID: lil-779027

ABSTRACT

Objective: to assess post-angioplasty myointimal hyperplasia in iliac artery of rabbits treated with extract of Moringa oleifera leaves. Methods : we conducted a randomized trial in laboratory animals for five weeks of follow-up, developed in the Vivarium of Pharmaceutical Technology Laboratory of the Universidade Federal da Paraíba. We used rabbits from the New Zealand breed, subjected to a hypercholesterolemic diet and angioplasty of the external iliac artery, randomized into two groups: M200 Group (n=10) - rabbits treated with 200mg/kg/day of Moringa oleifera leaves extract orally; SF group (n=10) - rabbits treated with 0.9% saline orally. After five weeks, the animals were euthanized and the iliac arteries prepared for histology. Histological sections were analyzed by digital morphometry. Statistical analysis was performed using the Student's t test. The significance level was 0.05. Results : there was no significant difference in myointimal hyperplasia between M200 and SF groups when comparing the iliac arteries submitted to angioplasty. Conclusion : there was no difference of myointimal hyperplasia between groups treated with saline and Moringa oleifera after angioplasty.


Objetivo: determinar a diferença da média de hiperplasia miointimal pós-angioplastia na artéria ilíaca de coelhos tratados e não tratados com extrato das folhas de Moringa oleifera. Métodos: ensaio aleatório em animais de laboratório por cinco semanas de seguimento, desenvolvido no Biotério do Laboratório de Tecnologia Farmacêutica da Universidade Federal da Paraíba. Foram utilizadas coelhas da raça Nova Zelândia, submetidas à dieta hipercolesterolêmica e angioplastia da artéria ilíaca externa, randomizadas em dois grupos: Grupo M200 (n=10), coelhas tratadas com 200mg/kg/dia de extrato de folhas de Moringa oleifera, por via oral; Grupo SF (n=10), coelhas tratadas com soro fisiológico 0,9%, por via oral. Após cinco semanas, os animais foram eutanaziados e as artérias ilíacas preparadas para histologia. Os cortes histológicos foram analisados por morfometria digital. A análise estatística foi realizada com o teste t de Student. O nível de significância foi 0,05. Resultados: comparando as artérias ilíacas submetidas à angioplastia do grupo M200 com as do grupo SF, não houve diferença significativa da hiperplasia miointimal Conclusão: não houve diferença da hiperplasia miointimal nos grupos tratados com soro fisiológico e Moringa oleifera após angioplastia.


Subject(s)
Animals , Female , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Plant Extracts/therapeutic use , Tunica Intima/pathology , Angioplasty/adverse effects , Moringa oleifera , Iliac Artery/pathology , Phytotherapy , Rabbits , Random Allocation , Hyperplasia/etiology , Hyperplasia/prevention & control
13.
Chinese Journal of Cardiology ; (12): 27-31, 2016.
Article in Chinese | WPRIM | ID: wpr-317651

ABSTRACT

<p><b>OBJECTIVE</b>To explore the related factors of optical coherence tomography (OCT) detected in-stent heterogeneous neointimal in coronary stents.</p><p><b>METHODS</b>A total of 143 cases of coronary heart disease patients with OCT detected in-stent neointimal hyperplasia in Fuwai hospital from September 2009 to April 2012 were included in this study and patients data were retrospectively analyzed. Patients were divided into heterogeneous intima group(26 cases) and homogeneous intima group(117 cases)according to neointimal characteristics. Clinical features and OCT characteristics of the 2 groups were compared and binary logistic regression analysis was performed to analyze the risk factors of in-stent heterogonous neointimal hyperplasia.</p><p><b>RESULTS</b>Compared to homogeneous intima group, patients in heterogeneous intima group had significantly higher cholesterol level ((5.31±1.11)mmol/L vs.(4.70±0.94)mmol/L, P=0.005), low-density lipoprotein cholesterol level ((2.57±0.87)mmol/L vs.(2.29±0.46)mmol/L, P=0.021) and triglyceride level (2.12(1.82-2.87)mmol/L vs. 1.90(1.73-2.11)mmol/L, P=0.015). Moreover, the percent of percutaneous coronary intervention (PCI) because of acute coronary syndrome (23.1%(6/26) vs. 6.8%(8/117), P=0.022) and the thin cap neoatheroma (5.8%(28/481)vs. 3.9%(89/2 276), P=0.043) were also significantly higher in heterogeneous intima group than in homogeneous intima group. Binary logistic regression analysis showed that low-density lipoprotein cholesterol (OR=2.74, 95%CI 1.04-7.24, P=0.042), triglyceride (OR=2.88, 95%CI 1.05-7.89, P=0.040), PCI for acute coronary syndrome (OR=12.74, 95%CI 2.69-60.49, P=0.001), and cerebrovascular disease (OR=13.09, 95%CI 2.16-79.53, P=0.005) were risk factors for in-stent heterogenous intima. Time post stent implantation was protective factor for in-stent heterogenous intima (OR=0.63, 95%CI 0.42-0.96, P=0.033).</p><p><b>CONCLUSION</b>OCT detected heterogeneous intima is correlated with level of blood lipid, PCI for acute coronary syndrome and history of cerebrovascular disease, and it may lead to unstable intima.</p>


Subject(s)
Acute Coronary Syndrome , Coronary Artery Disease , Humans , Hyperplasia , Neointima , Percutaneous Coronary Intervention , Retrospective Studies , Risk Factors , Stents , Tomography, Optical Coherence , Tunica Intima
14.
Article in English | WPRIM | ID: wpr-238413

ABSTRACT

The histopathological features of the middle cerebral artery (MCA) and superficial temporal artery (STA) from moyamoya disease (MMD) and their relationships with gender, age, angiography stage were explored. The causes and the clinical significance of vasculopathy of STA were also discussed. The clinical data and specimens of MCA and STA from 30 MMD patients were collected. Twelve samples of MCA and STA from non-MMD patients served as control group. Histopathological examination was then performed by measuring the thickness of intima and media, and statistical analysis was conducted. The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group. There was no significant pathological difference between the hemorrhage group and non-hemorrhage group, and between the males and females in MMD patients. Neither the age nor the digital subtraction angiography (DSA) stage was correlated with the thickness of intima in MCA and STA. MMD is a systemic vascular disease involving both intracranial and extracranial vessels. Preoperative external carotid arteriography, especially super-selective arteriography of the STA, benefits the selection of donor vessel.


Subject(s)
Adult , Angiography , Case-Control Studies , Female , Humans , Male , Middle Aged , Middle Cerebral Artery , Diagnostic Imaging , Pathology , Moyamoya Disease , Diagnostic Imaging , Pathology , General Surgery , Temporal Arteries , Diagnostic Imaging , Pathology , Tunica Intima , Diagnostic Imaging , Pathology
15.
Acta Physiologica Sinica ; (6): 592-610, 2016.
Article in Chinese | WPRIM | ID: wpr-331626

ABSTRACT

Vascular calcification is an active, invertible and highly regulated pathophysiological process, characterized by the deposition of hydroxyapatite crystal in vascular wall. Vascular calcification is classified into two types based on the sites of calcification: intimal atherosclerotic calcification and Mönckeberg's medial calcification. Medial vascular calcification is a pathological phenomenon commonly existed in diabetes, chronic kidney failure and aging. The current review summarizes the mechanisms of medial vascular calcification.


Subject(s)
Calcinosis , Humans , Tunica Intima , Vascular Calcification
16.
Arq. bras. cardiol ; 105(2): 176-183, Aug. 2015. tab, graf, ilus
Article in English | LILACS | ID: lil-758005

ABSTRACT

AbstractIntroduction:Cardiac allograft vasculopathy (CAV) is a major limitation for long-term survival of patients undergoing heart transplantation (HT). Some immunosuppressants can reduce the risk of CAV.Objectives:The primary objective was to evaluate the variation in the volumetric growth of the intimal layer measured by intracoronary ultrasound (IVUS) after 1 year in patients who received basiliximab compared with that in a control group.Methods:Thirteen patients treated at a single center between 2007 and 2009 were analyzed retrospectively. Evaluations were performed with IVUS, measuring the volume of a coronary segment within the first 30 days and 1 year after HT. Vasculopathy was characterized by the volume of the intima of the vessel.Results:Thirteen patients included (7 in the basiliximab group and 6 in the control group). On IVUS assessment, the control group was found to have greater vessel volume (120–185.43 mm3 vs. 127.77–131.32 mm3; p = 0.051). Intimal layer growth (i.e., CAV) was also higher in the control group (27.30–49.15 mm3 [∆80%] vs. 20.23–26.69 mm3[∆33%]; p = 0.015). Univariate regression analysis revealed that plaque volume and prior atherosclerosis of the donor were not related to intima growth (r = 0.15, p = 0.96), whereas positive remodeling was directly proportional to the volumetric growth of the intima (r = 0.85, p < 0.001).Conclusion:Routine induction therapy with basiliximab was associated with reduced growth of the intima of the vessel during the first year after HT.


ResumoFundamento:A doença vascular do enxerto (DVE) constitui uma grande limitação de sobrevida a longo prazo de pacientes submetidos a transplante cardíaco (TxC). Alguns imunossupressores diminuem o aparecimento da DVE.Objetivos:O principal objetivo foi avaliar, através de ultrassonografia intracoronária (USIC), a variação do crescimento volumétrico da camada íntima e comparar, após um ano, o grupo que recebeu basiliximab com um grupo de controle.Métodos:Treze pacientes de um único centro foram analisados retrospectivamente de 2007 a 2009. As análises foram feitas através de USIC, medindo-se o volume de um segmento coronariano nos primeiros 30 dias e um ano após o TxC. A vasculopatia foi caracterizada pelo volume da camada íntima do vaso.Resultados:O estudo incluiu 13 pacientes (7 no grupo com o basiliximab e 6 no grupo de controle). A análise por USIC revelou que o grupo de controle apresentou maior crescimento volumétrico do vaso (131,32 a 127,77 mm3 x 120 a 185,43 mm3 p = 0,051). O crescimento da camada íntima (CCI) também foi maior no grupo de controle [Basiliximab: 20,23 a 26,69 mm3 (∆ 33%); Controle: 27,30 a 49,15 mm3(∆ 80% p = 0,015)]. De acordo com a regressão univariada, o volume da placa aterosclerótica prévia do doador não teve relação com o crescimento da íntima (r = 0,15, p = 0,96), enquanto que o remodelamento positivo do vaso foi diretamente proporcional ao crescimento da íntima (r = 0,85, p < 0,001).Conclusão:A terapia de indução de rotina com basiliximab está associada à redução do crescimento da camada íntima do vaso no primeiro ano após o transplante cardíaco.


Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Antibodies, Monoclonal/therapeutic use , Coronary Artery Disease/drug therapy , Graft Rejection/drug therapy , Heart Transplantation/adverse effects , Immunosuppressive Agents/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Allografts/drug effects , Allografts/pathology , Biopsy , Case-Control Studies , Coronary Artery Disease/pathology , Coronary Artery Disease/prevention & control , Coronary Artery Disease , Disease Progression , Graft Rejection/pathology , Graft Rejection/prevention & control , Graft Rejection , /antagonists & inhibitors , Plaque, Atherosclerotic/drug therapy , Plaque, Atherosclerotic/pathology , Retrospective Studies , Risk Factors , Statistics, Nonparametric , Time Factors , Treatment Outcome , Tunica Intima/drug effects , Tunica Intima/pathology
17.
Arq. bras. med. vet. zootec ; 67(3): 747-754, May-Jun/2015. graf
Article in Portuguese | LILACS | ID: lil-753919

ABSTRACT

As lesões coronarianas já foram relatadas em espécies de peixes anádromos, com características semelhantes às observadas em aterosclerose humana, mas não em peixes cultivados sem interferência de padrões reprodutivos. Objetivou-se descrever lesões coronarianas em beijupirá (Rachycentron canadum) criado em sistema offshore, em 54 exemplares coletados ao longo do cultivo de oito meses. Amostras de tecido cardíaco de alevinos e juvenis foram submetidas à análise histopatológica e à microscopia eletrônica de transmissão (MET), para visualização de lesões coronarianas, sendo as lâminas histológicas coradas pela técnica de hematoxilina-eosina, ácido periódico de Schiff, alcian blue e reticulina de Gomori. Exames realizados pela fotomicroscopia de luz evidenciaram lesões arteriais caracterizadas por hiperplasia das túnicas íntima e média de artérias coronárias em, respectivamente, 29,63% e 79,63% dos animais, com redução do lúmen arterial. Na MET, foram observadas alterações na estrutura das coronárias com espessamento do endotélio e membrana basal, proliferação de fibroblastos e fibras colágenas, com acúmulo de material lipídico subendotelial, resíduos celulares aderidos à membrana basal e vesículas pinocitóticas com presença de lisossomos isolados. Constatou-se que os peixes da espécie Rachycentron canadum criados em cativeiro desenvolvem lesão arterial do tipo crônica degenerativa inflamatória.


The coronary lesions have been reported in species of anadromous fish with similar characteristics as those observed in human atherosclerosis, but not in farmed fish without interference of reproductive patterns. This study aimed to describe coronary lesions in beijupirá (Rachycentron canadum) farmed in an offshore system, in 54 specimens collected along an eight month cultivation period. Samples of heart tissue of fry and juveniles were subjected to histopathological analysis and transmission electron microscopy (TEM) for visualization of coronary lesions, the histology slides were stained using hematoxylin-eosin, periodic acid Schiffh, alcian blue, and reticulin of Gomori. Examinations performed by light microscopy showed arterial lesions characterized by hyperplasia of the intima and media tunics, respectively in 29.63% and 79.63 % of the animals, with reduced lumen. In TEM changes in the structure of the coronary endothelium and thickening of the basement membrane, proliferation of fibroblasts and collagen fibers, with subendothelial accumulation of lipid material, cellular debris adhering to the basement membrane and presence of pinocytotics vesicles and isolated lysosomes were observed. It has been found that the Rachycentron canadum fish species farmed in captivity develop arterial lesion of the chronic inflammatory degenerative type.


Subject(s)
Animals , Coronary Artery Disease/veterinary , Perciformes , Tunica Intima/pathology , Tunica Media/pathology , Stress, Physiological/physiology , Microscopy, Electron, Transmission/veterinary , Histological Techniques/veterinary , Coronary Vessels/pathology
18.
Rev. bras. cir. cardiovasc ; 30(1): 93-103, Jan-Mar/2015. tab, graf
Article in English | LILACS | ID: lil-742896

ABSTRACT

Objective: A systematic analysis was made in view of the epidemiology, clinical features, diagnosis, treatment and main outcomes of mycobacterial endocarditis. Methods: The data source of the present study was based on a comprehensive literature search in MEDLINE, Highwire Press and Google search engine for publications on mycobacterial endocarditis published between 2000 and 2013. Results: The rapidly growing mycobacteria become the predominant pathogens with Mycobacterium chelonae being the most common. This condition has changed significantly in terms of epidemiology since the 21st century, with more broad patient age range, longer latency, prevailed mitral valve infections and better prognosis. Conclusion: Mycobacterial endocarditis is rare and the causative pathogens are predominantly the rapidly growing mycobacteria. Amikacin, ciprofloxacin and clarithromycin are the most frequently used targeted antimicrobial agents but often show poor responses. Patients with deep infections may warrant a surgical operation or line withdrawal. With periodic multidrug therapy guided by drug susceptibility testing, and surgical managements, patients may achieve good therapeutic results. .


Objetivo: Uma análise sistemática foi feita considerando epidemiologia, quadro clínico, diagnóstico, tratamento e principais resultados da endocardite micobacteriana. Métodos: Foi realizada uma pesquisa bibliográfica abrangente no MEDLINE, Highwire Press e no Google para publicações sobre endocardite micobacteriana, publicados entre 2000 e 2013. Resultados: As micobactérias de crescimento rápido tornam-se os patógenos predominantes, com Mycobacterium chelonae sendo a mais comum. Essa condição se alterou significativamente em termos de epidemiologia, desde o início do século 21, abrangendo faixa etária mais ampla, maior latência, prevalecendo infecções da valva mitral e melhor prognóstico. Conclusão: Endocardite micobacteriana é rara e os patógenos causadores são predominantemente as micobactérias de crescimento rápido. Amicacina, ciprofloxacina e claritromicina são os agentes antimicrobianos mais frequentemente utilizados, mas muitas vezes apresentam respostas pobres. Pacientes com infecções profundas podem justificar um procedimento cirúrgico ou retirada de linha. Com a poliquimioterapia periódica guiada por testes de sensibilidade às drogas, e abordagens cirúrgicas, os pacientes podem obter bons resultados terapêuticos. .


Subject(s)
Aged , Humans , Male , Middle Aged , Carotid Arteries , Carotid Artery Diseases/epidemiology , Carotid Artery Diseases , Tunica Intima , Tunica Media , Analysis of Variance , Alcohol Drinking/epidemiology , Logistic Models , Odds Ratio , Predictive Value of Tests , Prevalence , Risk Assessment , Risk Factors , Russia/epidemiology
19.
Chinese Journal of Cardiology ; (12): 248-253, 2015.
Article in Chinese | WPRIM | ID: wpr-328780

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of NF-κB/survivin signal pathway in the intima hyperplasia of rat carotid balloon injury restenosis model.</p><p><b>METHODS</b>NF-κB siRNA lentivirus vector (titer was 1 × 10⁸ TU/ml) was established. Carotid balloon injury restenosis model was made in 33 SD rats. The rats were divided into 4 groups according to different processing methods, including negative control (NC) group (n = 11), NF-κB siRNA group (n =11), NF-κB siRNA+YM155 (survivin inhibitor) (n = 11), the uninjured carotid artery served as the normal control group (n = 11). After 7 days, the carotid sample (n = 5 each group) were harvested to detect the NF-κB and survivin mRNA expression by RT-PCR.The carotid sample were harvested on 28 days (n = 6 each group) for HE staining and measuring intima hyperplasia. Immunohistochemical method was also used to detect the expression of intima proliferation cell nuclear antigen (PCNA) and media α-SM-actin.</p><p><b>RESULTS</b>(1) After 7 days, NF-κB and survivin mRNA expression was significant higher in NC group than in normal control group (P<0.05), the NF-κB mRNA expression was significantly lower in NF-κB siRNA group than in NC group (P<0.05) and similar between NF-κB siRNA group and NF-κB siRNA+YM155 group. The survivin mRNA expression was significantly lower in NF-κB siRNA group compared to NC group (P<0.05) and significantly higher in NF-κB siRNA group than in NF-κB siRNA+YM155 group (P<0.05). (2) After 28 days, intima hyperplasia was observed in NC (0.13 ± 0.01), NF-κB siRNA (0.11 ± 0.01) and NF-κB siRNA+YM155 group (0.09 ± 0.01) mm² (P<0.05). Media area was similar among NC group, NF-κB siRNA group and NF-κB siRNA+YM155 group (P>0.05). I/M ratio was gradually reduced among NC group (1.55 ± 0.07), NF-κB siRNA group (0.92 ± 0.08), NF-κB siRNA+YM155 group (0.76 ± 0.06, all P<0.05). Similar results were found in the residual restenosis rate: NC group (58.71 ± 0.02) %, NF-κB siRNA group (32.13 ± 0.05) %, NF-κB siRNA+YM155 group (26.42 ± 0.03) % (all P<0.05) and expression of vascular smooth muscle cell PCNA: NC group (45.32 ± 7.21) %, NF-κB siRNA group (36.54 ± 6.42) %, NF-κB siRNA+YM155 group (28.57 ± 6.31) % (all P<0.05). On the contrary, the IOD of α-SM-actin in media increased gradually: NC group (0.055 ± 0.006), NF-κB siRNA group (0.072 ± 0.011), NF-κB siRNA+YM155 group (0.084 ± 0.008, all P<0.05).</p><p><b>CONCLUSION</b>Inhibiting NF-κB expression can significant decrease intima hyperplasia in this model, and this effect may be mediated by inhibiting survivin and reducing the proliferation of vascular smooth muscle cells.</p>


Subject(s)
Animals , Carotid Arteries , Carotid Artery, Common , Carotid Stenosis , Cell Proliferation , Disease Models, Animal , Endothelium, Vascular , Hyperplasia , Microtubule-Associated Proteins , Muscle, Smooth, Vascular , Myocytes, Smooth Muscle , NF-kappa B , Proliferating Cell Nuclear Antigen , RNA, Small Interfering , Rats , Rats, Sprague-Dawley , Signal Transduction , Tunica Intima
20.
Article in English | WPRIM | ID: wpr-30208

ABSTRACT

Neointimal proliferation after vascular injury is a key mechanism of restenosis, a major cause of percutaneous transluminal angioplasty failure and artery bypass occlusion. Emodin, an anthraquinone with multiple physiological activities, has been reported to inhibit proliferation of vascular smooth muscle cells (VSMCs) that might cause intimal arterial thickening. Thus, in this study, we established a rat model of balloon-injured carotid artery and investigated the therapeutic effect of emodin and its underlying mechanism. Intimal thickness was analyzed by hematoxylin and eosin staining. Expression of Wnt4, dvl-1, beta-catenin and collagen was determined by immunohistochemistry and/or western blotting. The proliferation of VSMC was evaluated by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and electron microscopy. MicroRNA levels were quantified by real-time quantitative PCR. Emodin relieved injury-induced artery intimal thickness. Results of western blots and immunohistochemistry showed that emodin suppressed expression of signaling molecules Wnt4/Dvl-1/beta-catenin as well as collagen protein in the injured artery. In addition, emodin enhanced expression of an artery injury-related microRNA, miR-126. In vitro, MTT assay showed that emodin suppressed angiotensin II (AngII)-induced proliferation of VSMCs. Emodin reversed AngII-induced activation of Wnt4/Dvl-1/beta-catenin signaling by increasing expression of miR-126 that was strongly supported by transfection of mimic or inhibitor for miR-126. Emodin prevents intimal thickening via Wnt4/Dvl-1/beta-catenin signaling pathway mediated by miR-126 in balloon-injured carotid artery of rats.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Animals , Carotid Arteries/drug effects , Carotid Artery Injuries/drug therapy , Cell Proliferation/drug effects , Emodin/therapeutic use , Male , MicroRNAs/metabolism , Phosphoproteins/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Tunica Intima/drug effects , Wnt4 Protein/metabolism , beta Catenin/metabolism
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