Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai 200032, China.
Biochem Biophys Res Commun. 2011 Jan 7;404(1):28-33. doi: 10.1016/j.bbrc.2010.11.037. Epub 2010 Nov 19.
Angiotensin II (AngII) and its type receptor (AT1-R) play important roles in the development of cardiac hypertrophy. Low level of high density lipoprotein (HDL) is also an independent risk factor for cardiac hypertrophy. We therefore investigated in the present study whether HDL inhibits cardiac hypertrophy relatively to inhibition of AngII and AT1-R in both in vitro and in vivo experiments. Stimulation of cultured cardiomyocytes of neonatal rats with AngII for 24 h and infusion of AngII in mice for 2 weeks resulted in marked cardiac hypertrophic responses including increased protein synthesis, enlarged sizes of cardiomyocytes and hearts, upregulated phosphorylation levels of protein kinases and reprogrammed expression of specific genes, all of which were significantly attenuated by the treatment with HDL. Furthermore, AngII-treatment induced upregulation of AT-R expression either in cultured cardiomyocytes or in hearts of mice and HDL significantly suppressed the upregulation of AT1-R. Our results suggest that HDL may abrogate AngII-induced cardiac hypertrophy through downregulation of AT1-R expression.
血管紧张素 II（AngII）及其受体（AT1-R）在心肌肥厚的发展中起重要作用。低水平的高密度脂蛋白（HDL）也是心肌肥厚的一个独立危险因素。因此，我们在本研究中探讨了 HDL 是否通过抑制 AngII 和 AT1-R 在体外和体内实验中抑制心肌肥厚。用 AngII 刺激新生大鼠心肌细胞 24 小时，用 AngII 灌注小鼠 2 周，导致明显的心肌肥厚反应，包括蛋白合成增加、心肌细胞和心脏增大、蛋白激酶磷酸化水平上调和特定基因表达的重新编程，这些反应均被 HDL 治疗显著减弱。此外，AngII 处理诱导培养的心肌细胞或小鼠心脏中 AT-R 表达上调，HDL 显著抑制 AT1-R 的上调。我们的结果表明，HDL 可能通过下调 AT1-R 表达来消除 AngII 诱导的心肌肥厚。
