A nonobstructive condition: Medial arterial calcification / 中南大学学报(医学版)

Vascular calcification, including intimal and medial calcification, is closely associated with a significant increase in cardiovascular diseases. Although increased understandings were achieved, people still know much more about intimal calcification than medial calcification because the latter doesn't obstruct the arterial lumen, commonly considered as a non-significant finding. We clarified the pathologic characteristic of medial calcification, its difference from intimal calcification, principally focused on its clinical relevance, such as diagnosis, nosogenesis, and hemodynamics. We underline the importance of identifying and distinguishing medial calcification, understanding its effect to local/systematic arterial compliance, and relationship to diabetic neuropathy. Recent studies emphasize do not ignore its predictive role in cardiovascular mortality. It is of great clinical significance to summarize the mechanisms of occurrence, lesion characteristics, diagnostic methods, pathogenic mechanisms, hemodynamic changes, and the distinction as well as association of intimal calcification with intimal calcification.

Microscopic analysis of the myocardial bridges and their relationship with atheromatous plaque / Análisis microscópico de los puentes miocárdicos y su relación con la placa ateromatosa

SUMMARY: Most histopathological studies have reported that the segment of the coronary artery below the myocardial bridge does not present atheromatous plaque, while the segment proximal to the myocardial bridge may have it. The aim of this study was to evaluate the microscopic environment of myocardial bridges. This descriptive study was carried out with 60 hearts of individuals who underwent autopsy at the National Institute of Legal Medicine and Forensic Sciences in Bucaramanga-Colombia. For each specimen, the coronary arteries and their branches were dissected, removing the subepicardial adipose tissue to identify the myocardial bridges and obtain histological sections of the compromised arterial branches. The presence of myocardial bridges was observed in 22 hearts (36.7%) with a length of 17.31 + 4.41 mm and a thickness of 904.57 + 312.27 mm. The coronary vessel caliber at the prepontine level was 246.57 + 49.33 mm and was significantly higher than in the pontine (188.92 + 60.55 mm) and postpontin (190.40 + 47 mm) segments (p=0.001 for both values). Atheromatous plaque was observed in the prepontine segment in 12 cases (46.15 %) and in 8 samples (30.76%) at the pontine level, but in this segment, there was slight damage to the vascular endothelium, or phase I level. The thickness of the tunica intima in the cases with atheromatous plaque was 15.68 + 13.39 mm and that of the plaque-free segments was 5.10 + 4.40 mm (p=0.005), and in the pontine segment the overlying periarterial adipose tissue had a thickness of 72.01 + 69.44 mm, which was higher than the other three locations (p=0.005). The morphometry of the perivascular fat pad and the presence of phase I atheromatous plaque are the main contributions of this study to the histology of myocardial bridges.

RESUMEN: La mayoría de los estudios histopatológicos han reportado que el segmento de la arteria coronaria debajo del puente miocárdico no presenta placa ateromatosa, mientras que el segmento proximal al puente miocárdico puede tenerla. El objetivo de este estudio fue evaluar el entorno microscópico de los puentes miocárdico. Este estudio descriptivo se realizó con 60 corazones de individuos a quienes se les práctico autopsia en el Instituto Nacional de Medicina Legal y Ciencias Forenses de Bucaramanga-Colombia. Para cada espécimen se realizó disección de las arterias coronarias y sus ramas, eliminando el tejido adiposo subepicárdico para identificar los puentes miocárdicos y obtener secciones histológicas de las ramas arteriales comprometidas. Se observó presencia de puentes miocárdicos en 22 corazones (36,7 %) con una longitud de 17.31 + 4.41 mm y un espesor de 904.57 + 312.27 mm. El calibre del vaso coronario a nivel prepontino fue 246.57 + 49.33 mm y fue significativamente mayor que en el segmento pontino (188.92 + 60.55 mm) y pospontino (190.40 + 47 mm) (p=0.001 para ambos valores). Se observó placa ateromatosa en el segmento prepontino en 12 casos (46.15 %) y en 8 muestras (30.76%) al nivel pontino, pero en este segmento, correspondieron a fase I, con ligero daño en el endotelio vascular. El espesor de la túnica íntima en los casos con placa ateromatosa fue de 15.68 + 13.39 mm y de los segmentos libres de placa fue 5.10 + 4.40 mm (p=0.005) y en el segmento pontino el tejido adiposo periarterial suprayacente presento un espesor de 72.01 + 69.44 mm, el cual fue mayor a las otras tres ubicaciones (p=0.005). La morfometría de la almohadilla adiposa perivascular y la presencia de placa ateromatosa en fase I son los principales aportes de este estudio a la histología de los puentes miocárdicos.

Rapamycin Combined with α-Cyanoacrylate Contributes to Inhibiting Intimal Hyperplasia in Rat Models / Rapamicina em Combinação com α-Cianoacrilato Contribui à Inibição de Hiperplasia Intimal em Modelos em Ratos

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.

Vascular calcification and growth arrest specific protein 6 levels in chronic renal failure / Calcificación vascular y detención de crecimiento de proteína específica 6 niveles en insuficiencia renal crónica

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

Mesotelioma de túnica vaginal en paciente con hidrocele rápidamente progresivo / Mesothelioma of the Tunica Vaginalis in a Patient with Rapidly Progressive Hydrocele

El mesotelioma es una entidad poco común y agresiva que compromete el mesotelio, involucrando así los diferentes órganos cubiertos por membranas serosas. El mesotelioma de túnica vaginal es una neoplasia muy rara, con un cuadro clínico poco específico y de difícil diagnóstico con las técnicas imagenológicas actuales. Presentamos el caso de un paciente con hidrocele rápidamente progresivo que fue llevado a hidrocelectomía. Se realizó un diagnóstico histopatológico de mesotelioma epitelial maligno de túnica vaginal que requirió orquidectomía radical, hemiescrotomectomía y linfadenectomía retroperitoneal. A un año de seguimiento, el paciente no tiene evidencia de la enfermedad.

Mesothelioma is an uncommon and aggressive entity that compromises the mesothelium, thus involving the different organs covered by serous membranes. The mesothelioma of the tunica vaginalis is a very rare neoplasm, with a non-specific clinical picture and difficult diagnosis with current imaging techniques. We report the case of a patient with rapidly progressive hydrocele who was taken to hydrocelectomy. A histopathological diagnosis of epithelial mesothelioma of the tunica vaginalis was made, which required radical orchiectomy, hemiscrotectomy and retroperitoneal lymphadenectomy. At one year of follow-up, the patient has no evidence of the disease.

Medicinal Herbs Effective Against Atherosclerosis: Classification According to Mechanism of Action

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.

Effects of Rosuvastatin on Apolipoprotein J in Balloon-Injured Carotid Artery in Rats / Efeitos da Rosuvastatina sobre Apolipoproteína J em Artérias de Ratos Lesionadas com Balão

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.

Sudden Cardiac Death due to Coronary Fibromuscular Dysplasia: Case Report and Literature Review / 대한법의학회지

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.

Rutaecarpine Inhibits Intimal Hyperplasia in A Balloon-Injured Rat Artery Model / 中国结合医学杂志

<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>

The effect of local application of neutralizing antibody to interleukin-1B on the development of vein graft intimal hyperplasia

@#<p style="text-align: justify;"><strong>OBJECTIVE:</strong> Intimal hyperplasia (IH) remains one of the major obstacles to long term vein graft patency. IL-1B has been demonstrated to be one of the first inflammatory cytokines expressed in the rat vein graft model of IH and may be an important initiator of the sequence of events leading to the development of IH. This study was designed to establish the role of IL-1B by demonstrating the outcome of inhibiting its effects by the use of neutralizing antibodies on the development of IH in this model.</p><p style="text-align: justify;"><strong>METHODS:</strong> Rat epigastric vein to femoral artery interposition grafts were treated with neutralizing antibody to IL-1B suspended in pluronic gel and harvested at the end of one week and two weeks. The amount of intimal hyperplasia was measured at the anastomotic and midgraft regions.</p><p style="text-align: justify;"><strong>RESULTS:</strong> The amount of IH was less at the anastomotic and midgraft regions of the treated grafts at the end of one week (p<0.05), but did not differ significantly with the untreated group at the end of two weeks.</p><p style="text-align: justify;"><strong>CONCLUSION:</strong> Neutralizing antibody to IL-1B delivered locally retarded but did not prevent the occurrence of IH in vein grafts. The initiation of the cascade of events in the development of IH is affected in a major way , but not singularly by IL-1B</p>

Promoting Vasa Vasorum Neovascularization of Vein Grafts Extenuates Hypoxia of the Wall and Its Subsequent Influence on Intimal Hyperplasia / 中华医学杂志(英文版)

<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>

Vascular Calcification: Current Genetics Underlying This Complex Phenomenon / 中华医学杂志(英文版)

<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>

Heparin-derived oligosaccharide inhibits vascular intimal hyperplasia in balloon-injured carotid artery / 中国天然药物

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.

Allium sativum compared to cilostazol as an inhibitor of myointimal hyperplasia

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.

Iliac artery myointimal hyperplasia in rabbits submitted to angioplasty and treated with Moringa oleifera / Hiperplasia miointimal na artéria ilíaca em coelhos submetidos à angioplastia e tratados com Moringa oleifera

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.

Histopathological features of middle cerebral artery and superficial temporal artery from patients with moyamoya disease and enlightenments on clinical treatment / 华中科技大学学报（医学）（英德文版）

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.

Related factors of optical coherence tomography detected in-stent heterogonous neointima / 中华心血管病杂志

<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>

The mechanisms of medial vascular calcification / 生理学报

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.

Reduced Progression of Cardiac Allograft Vasculopathy with Routine Use of Induction Therapy with Basiliximab / Redução da Progressão da Doença Vascular do Enxerto Cardíaco com o Uso Rotineiro da Terapia de Indução com Basiliximab

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.