Role of Angiotensin II in Fibrous Tissue Formation Following Myocardial Infarction

Traditional views of circulating angiotensin (Ang) II have focused on its endocrine properties in classical target tissues (e.g., kidneys and vasculature), where resident cell populations express Ang II receptors. More recent evidence supports its role in nonclassical tissues (e.g., adipose and connective tissues). Moreover, de novo generation of Ang peptides by cellular constituents of these nonclassical tissues has drawn attention to autocrine and paracrine properties of Ang II mediated by AT1 receptor-ligand binding at these sites. Fibrous tissue formation, regulated by phenotypically transformed fibroblast-like cells termed myofibroblasts, represent such nonclassical tissue and cells. Herein we address a role for local Ang II in tissue repair following myocardial infarction. The article further draws attention to the importance of chronic elevations in circulating Ang II, associated with activation of the renin– angiotensin–aldosterone system, that promote unwanted cardiac fibrosis. Genetic risk for adverse cardiovascular structural remodeling and thereby such events as myocardial infarction, stroke, and hypertension may be related to iterations in genes encoding angiotensin-converting enzyme and angiotensinogen. Potentials for gene therapy that could prevent fibrosis and thereby be cardioprotective are also briefly considered.