ANGIOTENSIN-II-INDUCED EXPRESSION OF TRANSCRIPTION FACTORS PRECEDES INCREASE IN TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNA IN NEONATAL CARDIAC FIBROBLASTS

Angiotensin II (ANG II), a potent vasoconstricting peptide, may act as a growth factor for cardiac muscle cells and induce hypertrophy. We examined the molecular phenotype of neonatal rat cardiac fibroblasts in relation to ANG II by studying the expression pattern of three transcription factors (Egr-1, c-fos and c-jun) and the transforming growth factor-beta 1 (TGF-beta 1). ANG II did not affect cell proliferation and growth of serum deprived neonatal cardiac fibroblasts as predicted from their DNA and protein contents. The expression of Egr-1 and c-fos was induced as early as 15 min that reached maximal levels at 45 min and declined thereafter, whereas c-jun was induced at 45 min and remained elevated up to 2 hrs of ANG II addition. ANG II up-regulated the expression of TGF-beta 1, which became apparent after 1 hr of incubation and reached a plateau between 16-48 hrs. Our results indicate that ANG II transiently stimulates the expression of transcription factors,which may up-regulate TGF-beta 1, that in turn could contribute to the process of myocardial extra-cellular matrix remodeling in hypertrophy. (C) 1994 Academic Press, Inc.