Artemisinin Attenuates Post-Infarct Myocardial Remodeling by Down-Regulating the NF-κB Pathway

Artemisinin Attenuates Post-Infarct Myocardial Remodeling by Down-Regulating the NF-κB Pathway

YONGWEI GU,^1,2, XI WANG,^1,2, XIN WANG,^1,2 MINGJIE YUAN,^1,2 GANG WU,^1,2 JUAN HU,^1,2 YANHONG TANG^1,2 and CONGXIN HUANG^1,2

¹Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China
²Cardiovascular Research Institute of Wuhan University, Wuhan, P.R. China

Myocardial infarction (MI) leads to progressive left ventricular (LV) dilatation and is associated with interstitial fibrosis in the non-infarcted myocardium. The NF-κB signaling pathway plays an important role in ventricular remodeling after MI. Recent studies have indicated that the anti-malarial agent artemisinin can inhibit NF-κB activation, which may attenuate post-infarct myocardial remodeling. In this study, we investigated the effect of artemisinin on post-infarct myocardial remodeling using a rat model of MI. Adult male Sprague Dawley rats were divided into a sham group (n = 10) and MI groups that were treated either with oral gavage of artemisinin (75 mg/kg/day, n = 20) or vehicle (0.5% carboxymethyl cellulose, n = 20) three times a day for 4 weeks. Each treatment was started at 24 hours after ligation of the left anterior descending coronary artery. Four weeks after MI, the artemisinin-treated group showed a significantly improved survival rate compared with that of the vehicle-treated group (65% vs. 40%, P < 0.05). Although infarct size was similar in both groups, echocardiography showed significant improvements in cardiac function and left ventricular dimensions in the artemisinin-treated group. Moreover, the degree of myocardial fibrosis and elevated levels of fibrosis-related factors [transforming growth factor-β1, collagen type I, matrix metalloproteinase (MMP)-2 and MMP-9] in the non-infarcted myocardium were remarkably ameliorated by artemisinin (all P < 0.05). Importantly, artemisinin inhibited the NF-κB pathway by blocking IKBα phosphorylation. In conclusion, artemisinin may attenuate post-infarct myocardial remodeling by down-regulating the NF-κB pathway.

keywords —— artemisinin; cardiac function; myocardial infarction; nuclear factor-kappaB; ventricular remodeling

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Tohoku J. Exp. Med., 2012, 227, 161-170

Correspondence: Congxin Huang, M.D., Department of Cardiology, Renmin Hospital of Wuhan University and Cardiovascular Research Institute of Wuhan University, 238 Jiefang Road, Wuchang, Wuhan 430060, P.R. China.

e-mail: huangcongxing@yahoo.cn