Growth factor signaling in myocardial stress and fibrosis
Endothelial dysfunction, abnormal extracellular matrix production and cardiomyocyte hypertrophy are key elements of cardiovascular diseases, leading to impairment of left ventricular function. Sustained external load, in conditions such as hypertension, myocardial infarction or valvular disease, can evolve to a state of decompensated hypertrophy in a complicated progressive process known as myocardial remodeling. Remodeling involves rearrangement of the cardiomyocyte muscle fibers and alterations in cardiomyocyte metabolism, but also interstitial fibrosis, accumulation of extracellular matrix, and angiogenesis. Eventually, remodeling leads to heart failure. Non-muscle cells residing in the interstitium likely play important roles in both cardiac hypertrophy and heart failure.
Our aim is to investigate how growth factors regulate cardiomyocytes and the contribution of non-muscle cells to remodeling process. Our specific interest focuses on the actions of activins, bone morphogenetic proteins (BMP), and growth and differentiation factors (GDF), the members of the transforming growth factor-β (TGF) family of secreted growth factors. The effect of these factors on endothelial function and parenchymal cell homeostasis in the diseased myocardium remain mostly unknown.
By utilizing genetic and pharmacological tools in experimental models, we aim to identify the downstream signaling mechanisms of growth factors during myocardial ischemia-reperfusion injury and to investigate the role of growth factor signaling in development of cardiac hypertrophy, fibrosis and remodeling in the stressed myocardium. We also utilize human material to determine the role of these growth factors in cardiovascular diseases.
Please also see our extended research group home page: http://www.oulu.fi/mrc/research-groups/kerkela
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