Cardioprotective effects of exercise training: the importance of nitric oxide

Left ventricular remodeling after myocardial infarction is a compensatory mechanism, which serves to restore left ventricular pump function to normal levels. Despite the apparent appropriateness of the process, left ventricular remodeling after myocardial infarction is an independent risk factor for the development of angina pectoris and heart failure. In contrast, physiological left ventricular remodeling produced by regular exercise training is associated with a decreased risk for heart failure. This PhD-project focuses on the physiological, cellular and molecular basis for the differences in myocardial remodeling between exercise-induced and pathological left ventricular remodeling. In addition, we investigate how regular exercise training favorably influences the myocardial abnormalities associated with pathological left ventricular remodeling, in particular, the role of an increased nitric oxide production in the beneficial effects of exercise training. For this purpose, studies are performed in wild-type mice but also eNOS transgenic or knock-out mice. Specifically we test the hypothesis that eNOS overexpression mimics exercise training and that eNOS knock-out abrogates the beneficial effects of exercise training in mice with a myocardial infarction.

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