Angiotensin II type1 receptor regulation and differential trophic effects on rat cardiac myofibroblasts after acute myocardial infarction

Fibroblast growth in the scar and surviving tissue is a key element of the remodeling post myocardial infarction. The regulation of fibroblast growth alter acute myocardial infarction remains to be determined. Recently, Angio tensin II has been demonstrated to be a mitogen for neonatal cardiac fibrob lasts. In this study adult rat cardiac fibroblasts were isolated from diffe rent regions of the infarcted rat heart and Angiotensin II effects examined . Adult Wistar-rats were sham operated or left coronary artery ligated. Aft er 4 days, hearts were removed and fibroblasts from sham operated, infarct- and non-infarct regions of the left ventricle isolated. Radioligand bindin g studies were performed and cell number, cell area, total protein, and AT( 1) receptor mRNA after stimulation determined. Radioligand binding studies demonstrated that myofibroblasts expressed a single class of high affinity Angiotensin II AT(1) receptors. Myofibroblasts from the infarct area reveal ed a lower maximal binding capacity, compared to sham operated myocardium. Conversely, myofibroblasts from the non-infarct area had a higher expressio n of Angiotensin II AT(1) receptor mRNA compared to sham operated myofibrob lasts. Angiotensin Il (1 muM, 48 h) increased cell-number in sham operated and non-infarct, but not in infarct myofibroblasts. Angiotensin II elevated total protein in sham operated, non-infarct, and infarct myofibroblasts. I n addition, Angiotensin II increased cell area in sham operated and infarct myofibroblasts. These data demonstrate that Angiotensin II acted as a mito gen in sham operated and non-infarct myofibroblasts and stimulated hypertro phy in infarct myofibroblasts. These regional different effects of Angioten sin II might participate in the remodeling post myocardial infarction. J. C ell. Physiol. 187: 326-335, 2001. (C) 2001 Wiley-Liss, Inc.