Artemisinin attenuates post-infarct myocardial remodeling by down-regulating the NF-κB pathway.
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.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China.
Yongwei
Y
Gu
Xi
X
Wang
Xin
X
Wang
Mingjie
M
Yuan
Gang
G
Wu
Juan
J
Hu
Yanhong
Y
Tang
Congxin
C
Huang
D000818:Animals; D037621:Artemisinins / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D015153:Blotting, Western; D006332:Cardiomegaly / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D024042:Collagen Type I / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D005355:Fibrosis; D006439:Hemodynamics / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016019:Survival Analysis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects
D037621:Artemisinins; D024042:Collagen Type I; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D053773:Transforming Growth Factor beta1; D000072000:NF-KappaB Inhibitor alpha; C031327:artemisinin; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9