Effects Of Lycopene On Ventricular Remodeling And Cardiac Function In The Rat Model Of Myocardial Infarction

Myocardial infarction (MI) is the leading cause of mortality and disability for cardiovascular disease. Ventricular remodeling, a key role in development of heart failure, is a therapeutic target in myocardial infarction. Lycopene is one of the major carotenoids. A large number of studies have reported that lycopene has a protective effect on cardiovascular. High serum concentration is associated with markedly reduced risk of cardiovascular disease, neurodegenerative disorders, serum lipid oxidation and cancers. However, it is unknown whether lycopene improves ventricular remodeling after myocardial infarction. In this study, we attempt to investigate the cardioprotection of lycopene after myocardial infarction. The study was divided into three parts as bellow.Part I:Effects of lycopene on cardiac function in the rat model of myocardial infarctionObjective:To explore the effects of lycopene on cardiac function and ventricular remodeling after myocardial infarction.Methods:Rat MI model was established by Left anterior descending coronary artery ligation. After operation, rats received lycopene or saline. After28days, rats underwent echocardiography and hemodynamic detection, and were sacrificed. Cardiac pathology change was analyzed by HE staining.Results:Compared with the MI group, lycopene significantly improved histomorphology and cardiac function, and reduced infarct size after myocardial infarction.Conclusion:Lycopene improved the cardiac function and ventricular remodeling in MI rats. Part II:Effects of lycopene on inflammatory response and myocardial apoptosis in the rat model of myocardial infarctionObjective:Inflammatory response is the basic mechanism of the development of chronic heart failure. Cardiomyocyte apoptosis plays an important role in ventricular remodeling after MI. NF-κB pathway could promote inflammation and myocardial apoptosis. It had reported that Lycopene inhibited cigarette smoke extract-mediated NF-kB activation. Therefore, we hypothesized that lycopene may improve ventricular remodeling by NF-κB pathway. The purpose of this part study was to observe the effects of lycopene on macrophage infiltration, TNF-a expression, cardiomyocyte apoptosis and NF-κB signaling pathway.Methods:Rat MI model was established by Left anterior descending coronary artery ligation. After operation, rats received lycopene or saline. After28days, rats underwent echocardiography and hemodynamic detection, and were sacrificed. Immunohistochemistry analysis was observed to macrophage infiltration. The expression of TNF-a and caspase-3, and NF-κB pathway activation in ischemic zone surrounding MI were detected PCR and western blot analysis.Results:Lycopene reduced myocardial apoptosis and caspase-3expression, inhibited macrophage infiltration and TNF-a expression, and attenuated NF-κB signaling pathway activation in ischemic zone surrounding MI.Conclusion:Lycopene inhibited NF-κB signaling pathway to reduce cardiomyocyte apoptosis and inflammatory response after MI, which could be mechanism of cardioprotective effects of lycopene. Part Ⅲ:Effect of lycopene on myocardial fibrosis in the rat model of myocardial infarctionObjective:It had reported that lycopene inhibited cigarette smoke extract-mediated matrix metalloproteinase-9(MMP-9) activation, and alleviated bleomycin-mediated pulmonary fibrosis. We speculated that lycopene could inhibit myocardial fibrosis and improve ventricular remodeling after MI. The purpose of this part study is to observe the effect of lycopene on myocardial fibrosis and to explore the possible mechanisms involved.Methods:Rat MI model was established by Left anterior descending coronary artery ligation. After operation, rats received lycopene or saline. After28days lycopene or saline, rats underwent echocardiography and hemodynamic detection, and were sacrificed. Myocardial fibrosis was observed by Masson staining. I type collagen MMP-9and MAPK protein expression was detected in ischemic zone surrounding MI by western blot.Results:Compared with MI group, lycopene improved myocardial fibrosis, inhibited the expression of p38MAPK, MMP-9and I type collagen.Conclusion:Lycopene improved ventricular remodeling by inhibiting p38MAPK activation and MMP-9expression.