FIBRONECTIN ACCUMULATION WITHIN CARDIAC MYOCYTES IN RATS WITH ELEVATED PLASMA ANGIOTENSIN-II

Elevation in plasma angiotensin II (AngII) is associated with cardiac myocyte necrosis. Myocyte necrosis followed by wound healing and fibro sis represents a structural remodeling of the myocardium thought to co ntribute to abnormal myocardial function. Fibronectin (FN) is generall y considered an early component of the healing process that precedes c ollagen accumulation. To better understand the time course of this rem odeling process involving both cardiac myocytes and extracellular matr ix, (i.e., FN and collagen), we used two animal models: (1) endogenous activation of the reninangiotensin system by surgical induction of re novascular hypertension and (2) exogenous AngII administration (150 ng /min/kg). Animals were killed at different time points within the firs t two weeks. Both ''cellular'' (cFN) and ''plasma'' (pFN) FN immunolab eling were compared with collagen distribution (picrosirius red stain) , together with histopathologic (hematoxylin-eosin stain) and ultrastr uctural examination of cardiac myocytes. In each experimental group, t he pattern and time course of FN immunolabeling was coincident with hi stopathologic evidence of myocyte injury and/or remodeling. We found d ifferent patterns of FN labeling of cardiac myocytes: (a) homogenous i ntracellular 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; howeve r, cFN was less pronounced and not seen in mature scars. Ultrastructur al examination revealed different kinds of intramyocytic inclusions, c haracterized by vacuoles containing fibrillar/flocculent material, rem nants of unknown origin, or internalized capillaries. We conclude that FNs are markers of cardiac myocyte necrosis and early interstitial re modeling and that renovascular hypertension and AngII administration e xhibit the same time course and pattern of FN and collagen expression.