糖尿病性心肌病
下调和上调
内分泌学
免疫印迹
内科学
线粒体融合
融合蛋白
β氧化
心功能曲线
医学
受体
心肌病
化学
生物化学
心力衰竭
新陈代谢
重组DNA
线粒体DNA
基因
作者
Peng Wang,Rui Wei,Xiaona Cui,Zongxuan Jiang,Jin Yang,Lingyun Zu,Tianpei Hong
标识
DOI:10.1111/1753-0407.13458
摘要
Abstract Introduction The role of cardiac microvascular endothelial cells (CMECs) in diabetic cardiomyopathy is not fully understood. We aimed to investigate whether a glucagon receptor (GCGR) monoclonal antibody (mAb) ameliorated diabetic cardiomyopathy and clarify whether and how CMECs participated in the process. Research Design and Methods The db / db mice were treated with GCGR mAb or immunoglobulin G (as control) for 4 weeks. Echocardiography was performed to evaluate cardiac function. Immunofluorescent staining was used to determine microvascular density. The proteomic signature in isolated primary CMECs was analyzed by using tandem mass tag‐based quantitative proteomic analysis. Some target proteins were verified by using western blot. Results Compared with db / m mice, cardiac microvascular density and left ventricular diastolic function were significantly reduced in db / db mice, and this reduction was attenuated by GCGR mAb treatment. A total of 199 differentially expressed proteins were upregulated in db / db mice versus db / m mice and downregulated in GCGR mAb‐treated db / db mice versus db / db mice. The enrichment analysis demonstrated that fatty acid β‐oxidation and mitochondrial fusion were the key pathways. The changes of the related proteins carnitine palmitoyltransferase 1B, optic atrophy type 1, and mitofusin‐1 were further verified by using western blot. The levels of these three proteins were upregulated in db / db mice, whereas this upregulation was attenuated by GCGR mAb treatment. Conclusion GCGR antagonism has a protective effect on CMECs and cardiac diastolic function in diabetic mice, and this beneficial effect may be mediated via inhibiting fatty acid β‐oxidation and mitochondrial fusion in CMECs.
科研通智能强力驱动
Strongly Powered by AbleSci AI