de Lima Aline D, Guido Maria C, Tavares Elaine R, Carvalho Priscila O, Marques Alyne F, de Melo Marcelo D T, Salemi Vera M C, Kalil-Filho Roberto, Maranhão Raul C
Laboratory of Metabolism and Lipids, Heart Institute (InCor), Medical School Hospital, University of São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 44, Bl. 2, 1o.SS, São Paulo, SP, 05403-900, Brazil.
Heart Failure Unit and Clinical Cardiology Division, Heart Institute (InCor), Medical School Hospital, University of São Paulo, Av. Dr. Eneas de Carvalho Aguiar, 44, Bl. 2, 1o.SS, São Paulo, SP, 05403-900, Brazil.
Lipids. 2018 Feb;53(2):177-187. doi: 10.1002/lipd.12014. Epub 2018 Feb 2.
Left ventricular (LV) remodeling after myocardial infarction constitutes the structural basis for ventricular dysfunction and heart failure. The characterization underlying the expression of lipoprotein receptors in cardiac dysfunction is scarcely explored. The aim of this study was to analyze the status of lipoprotein receptors on the infarcted and noninfarcted areas of LV and to verify whether nanoparticles that mimic the lipid structure of low-density lipoprotein (LDL) and have the ability to bind to LDL receptors (LDE) are taken up more avidly by the noninfarcted LV. 13 male Wistar rats with left coronary artery ligation (myocardial infarction [MI]) and 12 animals with SHAM operation (SHAM) were used in this study. 6 weeks after the procedure, the quantification of low-density lipoprotein receptor (LDLR), LDL receptor-related protein 1 (LRP1), scavenger receptor-class B type I (SR-BI) lipoprotein receptors, and PCNA proliferation marker, and tissue uptake of radioactively labeled LDE were performed. Immunohistochemistry and Western blot analysis showed that LDLR, LRP1, SR-BI, and PCNA, expression in infarcted area of MI was remarkably higher than SHAM and noninfarcted subendocardial (SEN) and interstitial (INT) areas. In addition, in SEN noninfarcted area of MI, the presence of LDLR was about threefold higher than in SHAM SEN and INT noninfarcted areas. The LDE uptake of noninfarcted LV of MI group was about 30% greater than that of SHAM group. In conclusion, these findings regarding the status of lipoprotein receptors after MI induction could help to establish mechanisms on myocardial repairing. In conclusion, infarcted rats with LV dysfunction showed increased expression of lipoprotein receptors mainly in the infarcted area.
心肌梗死后左心室（LV）重构是心室功能障碍和心力衰竭的结构基础。心脏功能障碍中脂蛋白受体表达的潜在特征鲜有研究。本研究的目的是分析左心室梗死区和非梗死区脂蛋白受体的状态，并验证模拟低密度脂蛋白（LDL）脂质结构并能与LDL受体（LDE）结合的纳米颗粒是否被非梗死左心室更 avidly摄取。本研究使用了13只结扎左冠状动脉（心肌梗死[MI]）的雄性Wistar大鼠和12只假手术（SHAM）动物。术后6周，对低密度脂蛋白受体（LDLR）、LDL受体相关蛋白1（LRP1）、清道夫受体B1型（SR-BI）脂蛋白受体和PCNA增殖标志物进行定量，并进行放射性标记LDE的组织摄取实验。免疫组织化学和蛋白质印迹分析表明，MI梗死区的LDLR、LRP1、SR-BI和PCNA表达明显高于SHAM组以及非梗死心内膜下（SEN）和间质（INT）区。此外，在MI的SEN非梗死区，LDLR的存在比SHAM组的SEN和INT非梗死区高约三倍。MI组非梗死左心室的LDE摄取比SHAM组大约高30%。总之，这些关于MI诱导后脂蛋白受体状态的发现有助于建立心肌修复机制。总之，伴有左心室功能障碍的梗死大鼠主要在梗死区表现出脂蛋白受体表达增加。
