Fibronectin accumulation within cardiac myocytes in rats with elevated plasma angiotensin II

Abstract

Elevation in plasma angiotensin II (AngII) is associated with cardiac myocyte necrosis. Myocyte necrosis followed by wound healing and fibrosis represents a structural remodeling of the myocardium thought to contribute to abnormal myocardial function. Fibronectin (FN) is generally considered an early component of the healing process that precedes collagen accumulation. To better understand the time course of this remodeling process involving both cardiac myocytes and extracellular matrix, (i.e., FN and collagen), we used two animal models: (1) endogenous activation of the renin-angiotensin system by surgical induction of renovascular hypertension and (2) exogenous AngII administration (150 ng/min/kg). Animals were killed at different time points within the first two weeks. Both “cellular” (cFN) and “plasma” (pFN) FN immunolabeling were compared with collagen distribution (picrosirius red stain), together with histopathologic (hematoxylin-eosin stain) and ultrastructural examination of cardiac myocytes. In each experimental group, the pattern and time course of FN immunolabeling was coincident with histopathologic evidence of myocyte injury and/or remodeling. We found different patterns of FN labeling of cardiac myocytes: (a) homogenous intracellular distribution in necrotic myocytes, most obvious on days 1 and 2; (b) patchy intracellular distribution in nonnecrotic myocytes starting on day 4; and (c) marking internalized capillaries. Both FNs were codistributed throughout the myocardium of each ventricle; however, cFN was less pronounced and not seen in mature scars. Ultrastructural examination revealed different kinds of intramyocytic inclusions, characterized by vacuoles containing fibrillar/flocculent material, remnants of unknown origin, or internalized capillaries. We conclude that FNs are markers of cardiac myocyte necrosis and early interstitial remodeling and that renovascular hypertension and AngII administration exhibit the same time course and pattern of FN and collagen expression.