Pathogenic Origins of Fibrosis in the Hypertensive Heart Disease that Accompanies Aldosteronism

Cardiac fibrosis interferes with the structural homogeneity of the myocardium in hypertensive heart disease (HHD). Its morphologic presentations include: widely scattered microscopic scars which have replaced myocytes lost to necrosis; and a perivascular fibrosis of intramural coronary arteries. An animal model of aldosterone/salt treatment has been used to examine the pathogenic origins of myocyte necrosis and coronary vasculopathy. A common cellular/subcellular pathway involving parathyroid hormone-mediated, intracellular Ca2+ overload-induced, mitochondrial-derived oxidative stress was identified. Myofibroblasts and their secretome which includes de novo generation of angiotensin peptides, are responsible for fibrogenesis at these sites. Cardioprotection includes upstream prevention of myocyte loss and vascular remodeling or downstream ablation of myofibroblasts and ongoing fibrogenesis at these sites.