{"title":"Blockade by nifedipine of advanced glycation end product-induced CD40-CD40 ligand interaction in endothelial cells.","authors":"S Yamagishi, S Kikuchi, K Takenaka, M Takeuchi","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of accelerated atherosclerosis. There is a growing body of evidence that CD40-CD40 ligand (CD40L) interaction also plays an important role in atherogenesis. However, the effects of AGEs on CD40-CD40L signaling in endothelial cells (ECs) remain to be elucidated. In this study, we investigated (i) whether injection of AGE-proteins to normal rats stimulates CD40L expression on circulating platelets and (ii) whether AGEs up-regulate CD40 mRNA levels in cultured ECs. We further examined the effects of nifedipine, one of the most popular dihydropyridine-based calcium antagonists, on CD40 gene expression in AGE-exposed ECs. Platelet surface CD40L expression was increased in AGE-bovine serum albumin (AGE-BSA)-injected rats, compared with nonglycated BSA administration. AGEs were found to induce up-regulation of CD40 mRNA levels in ECs, which were significantly blocked by nifedipine. These results suggest that AGEs could enhance CD40-CD40L interaction, thereby promoting atherosclerosis in diabetes. Blockade of CD40-CD40L signaling in ECs may be a molecular target for the vasculoprotective property of nifedipine.</p>","PeriodicalId":11336,"journal":{"name":"Drugs under experimental and clinical research","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2005-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Drugs under experimental and clinical research","FirstCategoryId":"1085","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Advanced glycation end products (AGEs), the senescent macroprotein derivatives that form in increased amounts in diabetes, have been implicated in the pathogenesis of accelerated atherosclerosis. There is a growing body of evidence that CD40-CD40 ligand (CD40L) interaction also plays an important role in atherogenesis. However, the effects of AGEs on CD40-CD40L signaling in endothelial cells (ECs) remain to be elucidated. In this study, we investigated (i) whether injection of AGE-proteins to normal rats stimulates CD40L expression on circulating platelets and (ii) whether AGEs up-regulate CD40 mRNA levels in cultured ECs. We further examined the effects of nifedipine, one of the most popular dihydropyridine-based calcium antagonists, on CD40 gene expression in AGE-exposed ECs. Platelet surface CD40L expression was increased in AGE-bovine serum albumin (AGE-BSA)-injected rats, compared with nonglycated BSA administration. AGEs were found to induce up-regulation of CD40 mRNA levels in ECs, which were significantly blocked by nifedipine. These results suggest that AGEs could enhance CD40-CD40L interaction, thereby promoting atherosclerosis in diabetes. Blockade of CD40-CD40L signaling in ECs may be a molecular target for the vasculoprotective property of nifedipine.