title: Molecular and cellular mechanisms of induction and regression of cardiac fibrosis in various models of myocardial hypertrophy.
abstract: This review is the summary of our findings on collagen gene expression and regulation in ventricular myocardium in experimental animal models of cardiac hypertrophy and in cardiac fibroblasts in response to hormonal stimuli. Cardiac fibrosis, or accumulation of collagen in the myocardium, is seen in several models of cardiac hypertrophy, such as those induced by aging, pressure overload, and norepinephrine-induced hypertension. Results on collagen gene expression have indicated that initial up-regulation of collagen gene expression usually precedes collagen accumulation in hypertrophied heart in those models. Thyroid hormone-induced cardiac hypertrophy, however, is distinguished from those types of hypertrophy by the absence of fibrosis and by down-regulation of collagen gene expression in ventricular tissue. Our in vitro studies on cardiac fibroblasts indicate that absence of fibrosis in thyroid hormone-induced hypertrophy could be the result of an inhibitory effect of thyroid hormone on collagen gene expression at transcriptional levels. Thyroid hormone was also shown to cause regression of cardiac fibrosis in the heart of a genetic model of collagen overproduction, the tight skin (TSK) mouse. These findings indicate that cardiac fibrosis and cardiac hypertrophy are induced via different mechanisms and that presence of cardiac hypertrophy does not imply cardiac fibrosis. The findings on inhibitory effects of thyroid hormone on collagen gene expression further suggest that biological inhibitory pathways, such as hormonal regulation, could be activated to compensate for excessive collagen production or for diminished collagen degradation by cardiac fibroblasts in cases of predisposition to cardiac fibrosis.
authors.affiliation: From the Department of Anesthesiology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: M
authors.initials: M
authors.lastname: Eghbali