Remodeling of the myocardium and potential targets in the collagen degradation and synthesis pathways

Current Drug Targets. Cardiovascular & Haematological Disorders
Bodh I Jugdutt

Abstract

Remodeling of the myocardium is the major mechanism for disability and death in prevalent cardiovascular diseases such as hypertension, heart failure and myocardial infarction (MI). It is a complex process that involves changes in structure, shape and topography at the global level and changes in myocytes and non-myocytes at cellular and subcellular levels that impact negatively on function. Although the myocytes subserve the heart's pump function, the predominant cell type in the heart is the fibroblast (not the myocyte). The fibroblast's major role is deposition of the extracellular matrix (ECM) of which collagen is the principal component. The cardiac extracellular collagen matrix (ECCM) maintains structural and functional integrity, and contributes to coordinated mechanical action with every systole during life. Excessive collagen deposition or pathological fibrosis is an important contributor to left ventricular (LV) dysfunction and poor outcome in hypertension, MI and heart failure. It is also an important problem in the aging heart. Antifibrotic agents that target steps in the collagen synthesis and degradation pathways therefore represent promising strategies for these diseases. Because reparative fibrosis is an essenti...Continue Reading

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