Protective Effect of RA on Myocardial Infarction-Induced Cardiac Fibrosis via AT1R/p38 MAPK Pathway Signaling and Modulation of the ACE2/ACE Ratio
Protective Effect of RA on Myocardial Infarction-Induced Cardiac Fibrosis via AT1R/p38 MAPK Pathway Signaling and Modulation of the ACE2/ACE Ratio
复制标题
RA 通过 AT1R/p38 MAPK 通路信号传导和 ACE2/ACE 比率调节对心肌梗死诱发的心脏纤维化的保护作用。
DOI：
10.1021/acs.jafc.6b03001
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发表时间：
2016-09-07
影响因子：
6.1
通讯作者：
Fu, Fenghua
中科院分区：
文献类型：
--
作者：
Liu, Qaofeng;Tian, Jingwei;Fu, Fenghua
Rosmarinic acid (alpha-o-caffeoy1-3,4-dihydroxyphenyllactic acid, RA) is a major active constituent of Rosmarinus officinalis Linn. (rosemary) having significant anti-inflammatory, anti-apoptotic, and antioxidant effects. However, the cardioprotection of RA is still not understood. The present study was designed, for the first time, to investigate the cardioprotection of RA on myocardial infarction (MI)-induced cardiac fibrosis and to clarify the possible mechanisms. MI was induced in adult rats by left anterior descending coronary artery ligation, and animals were then administered RA (50, 100, or 200 mg/kg) by gavage. Compared with the model group, RA treatment ameliorated changes in the left ventricular systolic pressure (LVSP), +dp/dt(max), and -dp/dt(max) after 4 weeks. This was associated with attenuation of infarct size, collagen volume fraction (CVF), expression of collagen I, collagen III, alpha smooth muscle actin (alpha-SMA), and hydroxyproline (Hyp) concentrations. RA treatment was also associated with decreased angiotensin-converting enzyme (ACE) expression and increased ACE2 expression, as well as decreased expression of angiotensin type 1 receptor (AT1R) and phospho-p38 mitogen-activated protein kinase (p38 MAPK). Thus, RA can protect against cardiac dysfunction and fibrosis following MI, likely due to decreasing ACE expression and increasing ACE2 expression via the AT1R/p38 MAPK pathway.
