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.

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.

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.

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.

Hiperplasia em túnicas de artérias coronárias de beijupirás criados em sistema offshore / Hyperplasia in tunics of coronary arteries in beijupirá farmed in offshore system

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.

Intimal Hyperplasia in Loop-Injured Carotid Arteries Is Attenuated in Transglutaminase 2-Null Mice

Arterial restenosis frequently develops after open or endovascular surgery due to intimal hyperplasia. Since tissue transglutaminase (TG2) is known to involve in fibrosis, wound healing, and extracellular matrix remodeling, we examined the role of TG2 in the process of intimal hyperplasia using TG2-null mice. The neointimal formation was compared between TG2-null and wild-type (C57BL/6) mice by two different injury models; carotid ligation and carotid loop injury. In ligation model, there was no difference in intimal thickness between two groups. In loop injury model, intimal hyperplasia developed in both groups and the intimal/medial area ratio was significantly reduced in TG2-null mice (P = 0.007). TG2 was intensely stained in neointimal cells in 2 weeks. In situ activity of TG2 in the injured arteries steadily increased until 4 weeks compared to uninjured arteries. Taken together, intimal hyperplasia was significantly reduced in TG2-null mice, indicating that TG2 has an important role in the development of intimal hyperplasia. This suggests that TG2 may be a novel target to prevent the arterial restenosis after vascular surgery.

Ponte miocárdica associada a lesões cardiovasculares em bovinos adultos da raça Canchim / Myocardial bridge associated with cardiovascular injuries in bovines adult of Canchim race / Puente miocárdico asociado a lesiones cardiovasculares en bovinos adultos de la raza canchim

FUNDAMENTO: A influência que a ponte miocárdica exerce sobre a corrente sanguínea no curso do segmento arterial sob a ponte tem sido objeto de discussão pela comunidade científica. OBJETIVO: Comparar o tecido muscular ultraestrutural da ponte miocárdica e a parede ventricular; analisar o grau de lesão da camada íntima dos segmentos arteriais e investigar possíveis mudanças que podem preceder ou iniciar o processo de lesões ateroscleróticas. MÉTODOS: Quarenta corações bovinos da raça Canchim foram estudados em relação às alterações da camada íntima das artérias coronarianas nos diferentes segmentos de ponte miocárdica. Para o exame microscópico, foram feitas colorações por hematoxilina-eosina e fucsina-resorcina seguindo técnicas microscópicas convencionais. Para o exame de microscopia eletrônica, os segmentos da ponte miocárdica de doze corações bovinos Canchim foram coletados a partir da parede ventricular e da artéria coronariana e foram processados de acordo com técnicas convencionais. RESULTADOS: Na microscopia de luz, foi observada maior frequência de lesões em segmentos pré-ponte e pós-ponte da camada íntima, em comparação ao segmento ponte. Espessamentos da camada íntima foram seguidos por um desarranjo na lâmina limitante elástica interna. Essas células frequentemente apresentaram seus citoplasmas ingurgitados por gotas lipídicas, compondo as chamadas células de espuma. A microscopia eletrônica revelou que as fibras musculares da ponte miocárdica geralmente se unem de forma reta e lisa apresentando ramos laterais com um número maior de mitocôndrias no músculo ventricular do que na ponte. CONCLUSÃO: Há poucas diferenças entre os tecidos musculares estudados; lesões da camada íntima são menos frequentes em regiões da ponte em comparação com as regiões pré e pós-ponte.

BACKGROUND: The influence that myocardial bridge exercises over blood stream in the course of arterial segment under the bridge has been discussed by the scientific community. OBJECTIVE: To compare ultrastructural muscle tissue of myocardial bridge and the ventricular wall; to analyze the degree of injury to the tunica intima of the arterial segments, and look for possible changes that may precede or initiate the process of atherosclerotic lesions. METHODS: Forty Canchim bovine hearts were studied regarding alterations of the tunica intima from coronary arteries on the different myocardial bridge segments. For the microscopic examination, hematoxylin-eosin and fuchsin-resorcin staining following conventional microscope techniques were made. For the electronic microscopic examination, myocardial Bridge segments from twelve Canchim bovine hearts were collected from the ventricle wall and coronary artery and were processed according to conventional techniques. RESULTS: In the light microscopy, a higher frequency of lesions on prepontine and postpontine segments of the tunica intima was observed, compared to the pontine segment. Tunica intima thickenings were followed by a disarrangement on the internal elastic limitant lamina. These cells often presented their cytoplasmas engorged by lipidic drops, making up the so-called foam cells. Electronic microscopy revealed that the muscular fibers of the myocardial bridge are usually joined in a straight and smooth way presenting lateral branches with a greater number of mitochondria in the ventricular muscle than in the bridge. CONCLUSION: There are few differences between the muscle tissues studied; intimae lesions are less frequent in pontine regions compared to pre and post-pontine regions.

FUNDAMENTO: La influencia que el puente miocárdico ejerce sobre la corriente sanguínea en el transcurso del segmento arterial bajo el puente, ha sido objeto de discusión por parte de la comunidad científica. OBJECTIVO: Comparar el tejido muscular ultra estructural del puente miocárdico y la pared ventricular; analizar el grado de lesión de la capa íntima de los segmentos arteriales e investigar posibles cambios que pueden preceder o iniciar el proceso de lesiones ateroscleróticas. MÉTODO: Cuarenta corazones bovinos de la raza Canchim fueron estudiados con respecto a las alteraciones de la capa íntima de las arterias coronarias en los diferentes segmentos del puente miocárdico. Para el examen microscópico, se hicieron coloraciones por hematoxilina-eosina y fucsina-resorcina secundando las técnicas microscópicas convencionales. Para el examen de microscopía electrónica, los segmentos del puente miocárdico de doce corazones de bovinos de la raza Canchim, fueron recolectados así como de la pared ventricular y de la arteria coronaria y fueron procesados de acuerdo con las técnicas convencionales. RESULTADOS: En la microscopía de luz, observamos una mayor frecuencia de lesiones en segmentos de pre puente y pos-puente de la capa íntima, en comparación con el segmento puente. Los espesamientos de la capa íntima vinieron acompañados por un desarreglo en la lámina limitante elástica interna. Esas células a menudo presentan sus citoplasmas ingurgitados por gotas lipídicas, lo que compone las llamadas células de espuma. La microscopía electrónica reveló que las fibras musculares del puente miocárdico generalmente se unen de forma recta y lisa, presentando ramas laterales con un número mayor de mitocondrias en el músculo ventricular que en el puente. CONCLUSIONES: Existen pocas diferencias entre los tejidos musculares estudiados. Las lesiones de la capa íntima son menos frecuentes en las regiones del puente en comparación con las regiones pre y pos puente.

Arterial Stiffness is Associated With Diabetic Retinopathy in Korean Type 2 Diabetic Patients / 예방의학회지

OBJECTIVES: We evaluated the association between common carotid artery intima-media thickness (CCA-IMT), brachial-ankle pulse wave velocity (baPWV), carotid plaque, and peripheral arterial disease (PAD) as indicators of macroangiopathy and diabetic retinopathy as an indicator of microangiopathy in type 2 diabetic patients. METHODS: We analyzed 605 type 2 diabetic patients registered at a public health center in Korea. Following overnight fasting, venous blood and urine samples were collected and analyzed. The CCA-IMT, levels of carotid plaque, baPWV, and ankle-brachial index (ABI) of the subjects were assessed. We used non-mydriatic fundus photography to diagnose diabetic retinopathy. Multiple logistic regression analyses were used to evaluate the association between macroangiopathy and diabetic retinopathy. CCA-IMT and baPWV were divided into tertiles: CCA-IMT, 0.39 to 0.65 mm, 0.66 to 0.78 mm, and 0.79 to 1.30 mm; baPWV, 9.9 to 15.8 m/s, 15.9 to 18.9 m/s, and 19.0 to 38.0 m/s. RESULTS: The association between baPWV and diabetic retinopathy remained significant after adjustment, with an increasing odds ratio (OR) in the second tertile (OR, 2.41; 95% confidence interval [CI], 1.27 to 4.55) and the third tertile (OR, 4.63; 95% CI, 2.33 to 9.21). No significant differences were observed in carotid plaque, PAD, and each tertile of CCA-IMT. CONCLUSIONS: BaPWV was associated with diabetic retinopathy, while CCA-IMT, carotid plaque, and PAD were not. This study suggests that the association between macroangiopathy and microangiopathy may be attributable to functional processes rather than structural processes within the vascular system.

Carotid intima-media thickness correlation with lipid profile in patients with familial hypercholesterolemia versus controls

To determine the variations in carotid intima-media thickness [CIMT] in familial hypercholesterolemia [FH] patients and its use as predictive marker for premature cardiovascular diseases. National Institute of Cardiovascular Diseases and Dr. Ziauddin Hospital, Karachi, from June 2008 to October 2009. Familial hypercholesterolemia was clinically diagnosed by premature coronary diseases, xanthomas, arcus cornealis and family history of premature coronary heart diseases. Controls were age matched normal individuals without hypercholesterolemia. Their lipid profile was tested after overnight fasting. CIMT was measured in mm using B-mode ultrasonography using linear probe. Student t-test was applied to compare mean CIMT of cases and the control. The mean CIMT values of the FH cases were correlated with LDL using Pearson's correlation test. Forty cases with hypercholesterolemia gave consent to participate in the study. These patients had total cholesterol >200 mg/dL and LDL >/= 160 mg/dL as compared to twenty controls of similar age with total cholesterol

Manejo endovascular de las complicaciones agudas de la disección aórtica tipo B / Endovascular management of acute complications of type b aortic dissection

Background: Type B aortic dissection is usually managed by intensive care medical therapy and surgery is reserved for treating the complications that can occur during the evolution of a case. Aim: To assess the endovascular management of acute complications of type B aortic dissection and the closure of the intimal defect and aortic false lumen. Material and Methods: Retrospective analysis of 8 consecutive patients aged 40 to 57 years (seven males) treated for acute complications in the initial episode of a type B aortic dissection between August 2006 and July 2008. Results: Six/eight were known hypertensive patients. The indications for surgery were intractable pain in one, hypertension refractory to treatment in two and distal hypoperfusion in fve. Five patients required covering of the left subclavian artery ostium, without need for surgical repair. One patient was subjected to renal angioplasty and stenting. Technical success was achieved in all cases, with complete closure of the proximal aortic tear and thoracic aortic false lumen, although 7 of patients had a persistent distal aortic false lumen. One case had a transient lower limb paraparesis. No patient died. Conclusions: Endovascular treatment is effective in closing the aortic tear as well as the thoracic aortic false lumen in aortic type B dissections with a low complication rate. Due to the high frequency of distal aortic false lumen persistence, it is not a defnitive treatment for this condition but it is useful for the acute complications of the initial phase of type B aortic dissection.

A DNA enzyme targeting Egr-1 inhibits rat vascular smooth muscle cell proliferation by down-regulation of cyclin D1 and TGF-â1

We have demonstrated that a synthetic DNA enzyme targeting early growth response factor-1 (Egr-1) can inhibit neointimal hyperplasia following vascular injury. However, the detailed mechanism of this inhibition is not known. Thus, the objective of the present study was to further investigate potential inhibitory mechanisms. Catalytic DNA (ED5) and scrambled control DNA enzyme (ED5SCR) were synthesized and transfected into primary cultures of rat vascular smooth muscle cells (VSMCs). VSMC proliferation and DNA synthesis were analyzed by the MTT method and BrdU staining, respectively. Egr-1, TGF-â1, p53, p21, Bax, and cyclin D1 expression was detected by RT-PCR and Western blot. Apoptosis and cell cycle assays were performed by FACS. Green fluorescence could be seen localized in the cytoplasm of 70.6 ± 1.52 and 72 ± 2.73 percent VSMCs 24 h after transfection of FITC-labeled ED5 and ED5SCR, respectively. We found that transfection with ED5 significantly inhibited cultured VSMC proliferation in vitro after 24, 48, and 72 h of serum stimulation, and also effectively decreased the uptake of BrdU by VSMC. ED5 specifically reduced serum-induced Egr-1 expression in VSMCs, further down-regulated the expression of cyclin D1 and TGF-â1, and arrested the cells at G0/G1, inhibiting entry into the S phase. FACS analysis indicated that there was no significant difference in the rate of apoptosis between ED5- and ED5SCR-transfected cells. Thus, ED5 can specifically inhibit Egr-1 expression, and probably inhibits VSMC proliferation by down-regulating the expressions of cyclin D1 and TGF-â1. However, ED5 has no effect on VSMC apoptosis.

Correlation between Hyperghrelinemia and Carotid Artery Intima-Media Thickness in Children with Prader-Willi Syndrome

PURPOSE: Prader-Willi syndrome (PWS) is a genetic disorder characterized by childhood-onset obesity and endocrine dysfunction that leads to cardiovascular disability. The objective of the study is to assess the relationship between carotid intima-media thickness (IMT) and atherosclerotic risk factors. MATERIALS AND METHODS: Twenty-seven PWS children and 24 normal controls were enrolled. Correlations of IMT with atherosclerotic risk factors were assessed. RESULTS: IMTs in the PWS group did not differ from those in the controls (p = 0.172), although total ghrelin levels were higher in the PWS children (p = 0.003). The multivariate analysis revealed positive correlations between total ghrelin levels (rho = 0.489, p = 0.046) and IMT in the PWS group and between body mass index-standard deviation score (BMI-SDS) (rho = 0.697, p = 0.005) and IMT in the controls. CONCLUSION: Considering the positive correlation of IMT with total ghrelin levels and the high level of ghrelin in PWS children, a further study is warranted to evaluate the role of elevated ghrelin on atherosclerosis for PWS.

Association Between Meat Consumption and Carotid Intima-Media Thickness in Korean Adults with Metabolic Syndrome / 예방의학회지

OBJECTIVES: The effect of meat consumption on cardiometabolic risk has been continuously studied, but their associations are not conclusive. The aim of this study is to examine the association between the consumption of meat or red meat and carotid intima-media thickness (IMT) in healthy Korean adults. METHODS: This study evaluated 2374 community-dwelling adults (933 men and 1441 women) who were free of cardiovascular disease or cancer, living in a rural area in Korea. Total meat and red meat intakes were assessed with a validated 103 item-food frequency questionnaire. Carotid IMT was evaluated ultrasonographically, IMTmax was defined as the highest value among IMT of bilateral common carotid arteries. RESULTS: After adjustment for potential confounding factors, the mean IMTmax tended to increase in higher meat consumption groups in both men and women with metabolic syndrome (p for trend= 0.027 and 0.049, respectively), but not in participants without metabolic syndrome. Frequent meat consumption (> or =5 servings/week) was significantly associated with higher IMTmax in men with metabolic syndrome (by 0.08 mm, p=0.015). Whereas, the association was not significant in women (by 0.05 mm, p=0.115). Similar but attenuated findings were shown with red meat intake. CONCLUSIONS: Our findings suggest that a higher meat consumption may be associated with a higher carotid IMT in Korean adults with metabolic syndrome. The frequent meat consumption (> or =5 servings/week), compared with the others, was associated with a higher carotid IMTmax only in men with metabolic syndrome. Further research is required to explore optimal meat consumption in people with specific medical conditions.

Modificación del grosor intima-media carotídeo según factores de riesgo clásicos y síndrome metabólico con o sin inflamación / Relation of intima-media thickness, traditional risk factors and metabolic syndrome in subjects with or without inflammation

El grosor intima-media carotideo (CIMT) es un marcador de aterosclerosis subclinica y eventos isquémicos cerebrales y coronarios. Si bien los valores normales promedio en Chile, han sido publicados, no existen datos locales de cómo se modifica el CIMT según la carga de factores de riesgo (FR) cardiovascular. Objetivos: Analizar la modificación del CIMT según la carga de FR clásicos, presencia de síndrome metabólico (SMET) y SMET más inflamación. Métodos: Hombres y mujeres de Santiago sin antecedente de eventos isquémicos previos, nivel socio económico medio, medio bajo y medio alto. En todos se realizó encuesta sobre antecedentes demográficos, FR cardiovascular, y medición de PA, IMC, cintura, y perfil lipídico, glicemia y proteína C-reactiva ultrasensible (ePCR) en ayuno. Para diagnóstico de SMET se usó NCEP ATPIII (2001), y para inflamación, ePCR> 2 mg/L (valor de corte de > riesgo porAHA). El CIMT se midió en carótida común derecha e izquierda con software MATH®. Resultados: Se incluyeron en el análisis 999 sujetos (508 hombres), edad promedio 43.8 +/- 11 años. La prevalencia de HTA fue 30 por ciento, dislipidemia 68 por ciento, tabaquismo 47 por ciento, y SMET 24 por ciento. El CIMT medio promedio fue 0.61 +/- 0.1 mm y la ePCR promedio 2.22 mg/L. La modificación del CIMT medio (mm) según número de FR (edad>45/55 hombre/mujer, diabetes, HTA, colesterol total > 200, HDL < 40/50, tabaquismo e historia familiar), fue la siguiente: 0 FR= 0.55 +/- 0.08; 1-2 FR= 0.59 +/- 0.091; > 3 FR= 0.67 +/- 0.12 (p < 0.0001). Asimismo, el CIMT aumentó según el puntaje de Framingham: < 5 por ciento = 0.58 +/- 0.09; 5-10 por ciento= 0.66 +/- 0.11; > 10-20 por ciento= 0.68 +/- 0.11; >20 por ciento > o = 0.76 +/- 0.14 (p < 0.0001). El CIMT fue significativamente mayor en los sujetos con SMET, y se incrementa en forma significativa cuando se adiciona ePCR>2 mg/L. En el modelo de regresión múltiple, el CIMT se asocia en forma conjunta a Framingham (p < 0.0001) y SMET+ePCR>2...

Carotid intima-media thickness (CIMT) is a marker for cerebral and coronary ischemic events. Normal values for CIMT in Chile have been published but the relation of CIMT to level of risk factors (RF) is unknown. Aim. To analyze the relation of CIMT to level of traditional RF and the presence of metabolic syndrome (MS), with or without inflammation. Methods. Males and females living in Santiago, Chile, with no prior history of ischemic events, of a low, medium or high socio-economic level, were studied. Demographic data, and presence of RF were obtained. Blood pressure, BMI, waist, blood lipids, blood glucose and US-CRP were measured in the fasting state. The presence of MS was defined by the NCEP-ATP III (2001) criteria. Inflammation was defined as US-CRP >2mg/L (the cut off point for increased risk, according to the AHA). CIMT was measure in both carotid arteries using the MATH® software. Results. 999 subjects (508 males), aged 43 +/- 11 years old. The prevalence of hypertension (HT) was 30 percent, dyslipidemia 68 percent, tobacco use 41 percent and MS 24 percent. Mean CIMT was 0.61 +/- 0.1 mm and US-PCR was 2.22 mg/L. CIMT according to number of RF - age > 45/55 (male/female), diabetes, HT, total cholesterol > 200 mg/dl, HDL < 40/50 mg/dl, tobacco use and family history- were: 0 RF: 0.55 +/- 0.08; 1-2 RF: 0.59 +/- 0.091; >3 RF: 0.67 +/- 0.12 (p < 0.0001). CIMT according to Framingham scores was: < 5 percent: 0.58 +/- 0.09; 5 - 10 percent: 0.66 +/- 0.11; 10 - 20 percent: 0.68 +/- 0.11 and > 20 percent: 0.76 +/- 0.14 (p < 0.0001). CIMT was significantly greater in subjects with MS and more in the group with US-PCR > 2mg/L. In multiple regression analysis, CIMT was jointly associated to Framingham score (p < 0.0001) and presence of MS + US-PCR >2 mg/L (p=0.01) (r2=0.19 for the model). Conclusion. CIMT increases in relation to traditional RF load and the presence of MS. An increased atherosclerotic risk in subjects with MS+inflammation (US-PCR > 2 mg/L)...

Complexo miointimal das carótidas comum e interna em portadores de esquistossomose mansônica hepatoesplênica / Intima-media thickness of common and internal carotid arteries in patients with hepatosplenic schistosomiasis mansoni

OBJETIVO: Avaliar a espessura do complexo miointimal (IMT) das carótidas comum e interna, em portadores de esquistossomose hepatoesplênica (EHE) não tratados cirurgicamente, já submetidos a cirurgia para descompressão do sistema porta por esplenectomia e ligadura da veia gástrica esquerda, e comparar com volutários de condições sócio-econômico-ambientais similares, não portadores de esquistossomose. MÉTODOS: Utilizando aparelho de ultra-som Doppler de 7,5MHz foram mensurados os IMT de três grupos de voluntários, de ambos os gêneros, com idades que variaram de 20 a 60 anos, sendo avaliados os IMT máximos, IMT médios, IMT mínimos e seus desvios-padrão, das carótidas comuns e internas e feitas as comparações entre os grupos e suas associações com fatores de risco: idade, hipertensão arterial e tabagismo. RESULTADOS: Não houve diferença significante na média dos IMT, entre os lados direito e esquerdo e nem entre os grupos. Nos pacientes tratados cirurgicamente, assim como nos indivíduos-controle confirmou-se a associação, já conhecida, com os fatores de risco para aterosclerose (idade, hipertensão arterial e tabagismo). Contudo, não se observou este comportamento nos pacientes não operados. CONCLUSÃO: A EHE sem tratamento cirúrgico parece conferir "alguma proteção" contra a aterogênese em seres humanos; todavia, os achados não dão suporte definitivo a esta hipótese.

OBJECTIVE: To evaluate the intima-media thickness (IMT) of common and internal carotid arteries in patients with hepatosplenic schistomiasis mansoni and those who underwent portal decompression surgery (splenectomy and left gastric artery ligature). Both groups were compared with a health volunteer control group, living in the same social-economic-environmental conditions. MEHTODS: An ultrasound Doppler with a 7.5 MHz probe was used. The IMT was measured in the three groups with 20 individuals each, of both gender, with ages ranging from 20 to 60 years. The mean and standard deviations of common and internal carotid arteries maxIMT, medIMT, minIMT were assessed. Risk factors: age, systemic arterial hypertension and cigarette smoking were investigated as regard to IMT measurements. RESULTS: There were no statistical differences in IMT between right and left side, and among surgical, non-surgical and control groups. The surgical treated patients and controls showed correlation to known atherosclerotic risk factors: age, hypertension and cigarette smoking. However, non-surgically treated patients did not present the same correlation. CONLCUSION: It is tempting to believe that non-operated schistosomotic patients may have "some protection" against atherogenesis in human beings; however, the data do not lend full support to this hypothesis.

Pitfalls in the assessment of murine atherosclerosis: [review]

This review provides examples of the fact that different procedures for the measurement of atherosclerosis in mice may lead to interpretation of the extent of atherosclerosis having markedly different biological and clinical significance for humans: 1) aortic cholesterol measurement is highly sensitive for the detection of early and advanced atherosclerosis lesions, but misses the identification of the location and complexity of these lesions that are so critical for humans; 2) the histological analysis of the aortic root lesions in simvastatin-treated and control mice reveals similar lesion morphology in spite of the remarkable simvastatin-induced reduction of the aortic cholesteryl ester content; 3) in histological analyses, chemical fixation and inclusion may extract the tissue fat and also shrink and distort tissue structures. Thus, the method may be less sensitive for the detection of slight differences among the experimental groups, unless a more suitable procedure employing physical fixation with histological sample freezing using optimal cutting temperature and liquid nitrogen is employed. Thus, when measuring experimental atherosclerosis in mice, investigators should be aware of several previously unreported pitfalls regarding the extent, location and complexity of the arterial lesion that may not be suitable for extrapolation to human pathology.

Normal flow-mediated vasodilatation of the brachial artery and carotid artery intima-media thickness in subclinical hypothyroidism

Subclinical hypothyroidism (SHT) is a disease for which exact therapeutic approaches have not yet been established. Previous studies have suggested an association between SHT and coronary heart disease. Whether this association is related to SHT-induced changes in serum lipid levels or to endothelial dysfunction is unclear. The aim of this study was to determine endothelial function measured by the flow-mediated vasodilatation of the brachial artery and the carotid artery intima-media thickness (IMT) in a group of women with SHT compared with euthyroid subjects. Triglycerides, total cholesterol, HDL-C, LDL-C, apoprotein A (apo A), apo B, and lipoprotein(a) were also determined. Twenty-one patients with SHT (mean age: 42.4 ± 10.8 years and mean thyroid-stimulating hormone (TSH) levels: 8.2 ± 2.7 µIU/mL) and 21 euthyroid controls matched for body mass index, age and atherosclerotic risk factors (mean age: 44.2 ± 8.5 years and mean TSH levels: 1.4 ± 0.6 µIU/mL) participated in the study. Lipid parameters (except HDL-C and apo A, which were lower) and IMT values were higher in the common carotid and carotid bifurcation of SHT patients with positive serum thyroid peroxidase antibodies (TPO-Ab) (0.62 ± 0.2 and 0.62 ± 0.16 mm for the common carotid and carotid bifurcation, respectively) when compared with the negative TPO-Ab group (0.55 ± 0.24 and 0.58 ± 0.13 mm, for common carotid and carotid bifurcation, respectively). The difference was not statistically significant. We conclude that minimal thyroid dysfunction had no adverse effects on endothelial function in the population studied. Further investigation is warranted to assess whether subclinical hypothyroidism, with and without TPO-Ab-positive serology, has any effect on endothelial function.

C-reactive Protein and Carotid Intima-media Thickness in a Population of Middle-aged Koreans / 예방의학회지

OBJECTIVES: This study was performed to evaluate the relationship between C-reactive protein (CRP) and carotid intima-media thickness (carotid IMT) in a population of middle-aged Koreans. METHODS: A total of 1,054 men and 1,595 women (aged 40-70 years) from Kanghwa County, Korea, were chosen for the present study between 2006 and 2007. We measured high-sensitivity CRP and other major cardiovascular risk factors including anthropometrics, blood pressure, blood chemistry, and carotid ultrasonography. Health related questionnaires were also completed by each study participant. Carotid IMT value was determined by the maximal IMT at each common carotid artery. The relationship between CRP level and carotid IMT was assessed using multiple linear and logistic regression models after adjustment for age, body mass index, menopause (women), systolic blood pressure, total/HDL cholesterol ratio, triglyceride level, fasting glucose, smoking, and alcohol consumption. RESULTS: Mean carotid IMT values from the lowest to highest quartile of CRP were 0.828, 0.873, 0.898, and 0.926 mm for women (p for trend<0.001), and 0.929, 0.938, 0.949, and 0.979 mm for men (p for trend=0.032), respectively. After adjustment for major cardiovascular risk factors, the relationship between CRP and carotid IMT was significant in women (p for trend=0.017), but not in men (p for trend=0.798). Similarly, adjusted odds ratio of increased IMT, defined as the sex-specific top quartile, for the highest versus lowest CRP quartiles was 1.55 (95% CI=1.06-2.26) in women, but only 1.05 (95% CI=0.69-1.62) in men. CONCLUSIONS: CRP and carotid IMT levels appear to be directly related in women, but not in men.

Association of Blood Pressure Levels with Carotid Intima-Media Thickness and Plaques / 예방의학회지

OBJECTIVES: The aim of this study was to investigate the association of blood pressure levels with the common carotid artery intima-media thickness (CCA-IMT) and carotid plaques. METHODS: Data were obtained from 2,635 subjects, aged 50 years and over, who participated in the Community Health Survey (a population-based, cross-sectional study) in Dong-gu, Gwangju city between 2007 and 2008. Participants were categorized into three groups according to blood pressure levels; normotensives ( or =140/90 mmHg). Prehypertensives were further categorized as low prehypertensives (120-129/80-84 mmHg) and high prehypertensives (130-139/85-89 mmHg). Carotid intima-media thickness and plaques were evaluated with a high-resolution B-mode ultrasound. Statistical analyses were performed using chi-square test, ANOVA, and multiple logistic regression. RESULTS: Prehypertensives had significantly greater maximal CCA-IMT values than normotensives, with a multivariate adjusted odds ratio of 1.78 (95% CI=1.36-2.32) for abnormal CCA-IMT (maximal CCA-IMT > or =1.0 mm), and 1.45 (95% CI=1.19-1.77) for carotid plaques. The multivariate adjusted odds ratio of low prehypertensives was 1.64 (95% CI=1.21-2.21) for abnormal CCA-IMT, and 1.30 (95% CI=1.04-1.63) for carotid plaques compared with normotensives. Subject with hypertension had higher frequency of abnormal CCA-IMT (odds ratio, 2.18; 95% CI=1.49-3.18), and carotid plaques (odds ratio, 1.98; 95% CI=1.46-2.67) compared with normotensives after adjustment for other cardiovascular risk factors. CONCLUSIONS: Our results indicate that there is a significant increase in the prevalence of carotid atherosclerosis in subjects with prehypertension (even in low prehypertensives) compared with normotensive subjects. Further studies are required to confirm the benefits and role of carotid ultrasonography in persons with prehypertension.