title: Dual ACE-inhibition and angiotensin II AT1 receptor antagonism with curcumin attenuate maladaptive cardiac repair and improve ventricular systolic function after myocardial infarctionin rat heart.
abstract: Curcumin has been shown to improve cardiac function by reducing degradation of extracellular matrix and inhibiting synthesis of collagen after ischemia. This study tested the hypothesis that attenuation of maladaptive cardiac repair with curcumin is associated with a dual ACE-inhibition and angiotensin II AT1 receptor antagonism after myocardial infarction. Sprague-Dawley rats were subjected to 45min ischemia followed by 7 and 42 days of reperfusion, respectively. Curcumin was fed orally at a dose of 150mg/kg/day only during reperfusion. Relative to the control animals, dietary treatment with curcumin significantly reduced levels of ACE and AT1 receptor protein as determined by Western blot assay, coincident with less locally-expressed ACE and AT1 receptor in myocardium and coronary vessels as identified by immunohistochemistry. Along with this inhibition, curcumin significantly increased protein level of AT2 receptor and its expression compared with the control. As evidenced by less collagen deposition in fibrotic myocardium, curcumin also reduced the extent of collagen-rich scar and increased mass of viable myocardium detected by Masson׳s trichrome staining. Echocardiography showed that the wall thickness of the infarcted anterior septum in the curcumin group was significantly greater than that in the control group. Cardiac contractile function was improved in the curcumin treated animals as measured by fraction shortening and ejection fraction. In cultured cardiac muscle cells, curcumin inhibited oxidant-induced AT1 receptor expression and promoted cell survival. These results suggest that curcumin attenuates maladaptive cardiac repair and enhances cardiac function, primarily mediated by a dual ACE-inhibition and AT1 receptor antagonism after myocardial infarction.
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Xue-Fen
authors.initials: XF
authors.lastname: Pang
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Li-Hui
authors.initials: LH
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, GA, USA.
authors.forename: Ning-Ping
authors.initials: NP
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Mercer University School of Medicine, Macon, GA, USA.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Ijaz Shah
authors.affiliation: Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, GA, USA.
authors.forename: Ron
authors.initials: R
authors.lastname: Garner
authors.affiliation: Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi, China; Cardiovascular Research Laboratory, Mercer University School of Medicine, Savannah, GA, USA. Electronic address: zhao_z@mercer.edu.
authors.forename: Zhi-Qing
authors.initials: ZQ
authors.lastname: Zhao
keywords: Angiotensin II AT(1) receptor; Angiotensin converting enzyme; Cardiac function; Cardiac repair; Collagen; Curcumin