Low density lipoprotein receptor-related protein 1 expression correlates with cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy patients.
Low density lipoprotein receptor-related protein 1 expression correlates with cholesteryl ester accumulation in the myocardium of ischemic cardiomyopathy patients.
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DOI：
10.1186/1479-5876-10-160
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发表时间：
2012-08-08
影响因子：
7.4
通讯作者：
Llorente-Cortés V
中科院分区：
文献类型：
--
作者：
Cal R;Juan-Babot O;Brossa V;Roura S;Gálvez-Montón C;Portoles M;Rivera M;Cinca J;Badimon L;Llorente-Cortés V
我们的假设是，某些脂蛋白受体的过度表达可能与人类缺血心肌中的脂质积聚有关。心肌内脂质超负荷可导致心肌收缩功能障碍和心律失常。因此，本研究的目的是评估高胆固醇血症LDL和高甘油三酯血症VLDL剂量对心肌细胞中LRP 1表达的影响，以及缺血性心肌病患者左心室组织中LRP 1表达与中性脂质蓄积之间的潜在相关性。细胞培养实验包括在常氧和低氧条件下暴露于脂蛋白的对照和LRP 1缺陷型心肌细胞。纳入了18例ICM患者和8例非病变心脏（CNT）的移植心脏。采用真实的时间PCR和Western blotting分析低密度脂蛋白受体相关蛋白1（LRP 1）、极低密度脂蛋白受体（VLDLR）和低密度脂蛋白受体（LDLR）的表达。脂质提取后，通过薄层色谱法测定胆固醇酯（CE）、甘油三酯（TG）和游离胆固醇（FC）含量。Western blotting实验显示，缺血心肌中LRP 1、VLDLR和HIF-1α蛋白水平显著上调。免疫组化和共聚焦显微镜分析显示ICM患者心肌细胞LRP 1和HIF-1α表达上调。体外研究表明，极低密度脂蛋白，低密度脂蛋白和缺氧对LRP 1的表达产生上调作用，LRP 1在心肌细胞脂蛋白胆固醇酯积累中起主要作用。心肌CE积聚与缺血心脏中LRP 1水平密切相关。综上所述，我们的研究结果表明，LRP 1上调是缺血性心脏心肌胆固醇酯蓄积的关键，LRP 1可能是预防缺血性心肌病心肌胆固醇蓄积有害作用的靶点。
Our hypothesis was that overexpression of certain lipoprotein receptors might be related to lipid accumulation in the human ischemic myocardium. Intramyocardial lipid overload contributes to contractile dysfunction and arrhythmias in cardiomyopathy. Thus, the purpose of this study was to assess the effect of hypercholesterolemic LDL and hypertrigliceridemic VLDL dose on LRP1 expression in cardiomyocytes, as well as the potential correlation between LRP1 expression and neutral lipid accumulation in the left ventricle tissue from ischemic cardiomyopathy patients. Cell culture experiments include control and LRP1-deficient cardiomyocytes exposed to lipoproteins under normoxic and hypoxic conditions. Explanted hearts from 18 ICM patients and eight non-diseased hearts (CNT) were included. Low density lipoprotein receptor-related protein 1 (LRP1), very low density lipoprotein receptor (VLDLR) and low density lipoprotein receptor (LDLR) expression was analyzed by real time PCR and Western blotting. Cholesteryl ester (CE), triglyceride (TG) and free cholesterol (FC) content was assess by thin layer chromatography following lipid extraction. Western blotting experiments showed that protein levels of LRP1, VLDLR and HIF-1α were significantly upregulated in ischemic hearts. Immunohistochemistry and confocal microscopy analysis showed that LRP1 and HIF-1α were upregulated in cardiomyocytes of ICM patients. In vitro studies showed that VLDL, LDL and hypoxia exerted an upregulatory effect on LRP1 expression and that LRP1 played a major role in cholesteryl ester accumulation from lipoproteins in cardiomyocytes. Myocardial CE accumulation strongly correlated with LRP1 levels in ischemic hearts. Taken together, our results suggest that LRP1 upregulation is key for myocardial cholesterol ester accumulation in ischemic human hearts and that LRP1 may be a target to prevent the deleterious effects of myocardial cholesterol accumulation in ischemic cardiomyopathy.
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影响因子：
8.7
作者：
Llorente-Cortés, V;Martínez-González, J;Badimon, L
通讯作者：
Badimon, L
影响因子：
5
作者：
Castellano, Jose;Farre, Jordi;Llorente-Cortes, Vicenta
通讯作者：
Llorente-Cortes, Vicenta
DOI：
10.1152/ajpendo.00273.2004
发表时间：
2005-06-01
影响因子：
5.1
作者：
Pillutla, P;Hwang, YYC;Goldberg, IJ
通讯作者：
Goldberg, IJ
影响因子：
37.8
作者：
StreaterKnowlen, IM;Evanochko, WT;Pohost, GM
通讯作者：
Pohost, GM
影响因子：
3.5
作者：
Chabowski, Adrian;Gorski, Jan;Bonen, Arend
通讯作者：
Bonen, Arend