Angiotensin II up‐regulates the expression of scleraxis in cardiac myofibroblasts isolated from the site of myocardial infarction

Scleraxis (scx) is a basic helix-loop-helix transcription factor involved in TGF-β1 induced collagen expression and fibrosis. Recent studies have implicated scx to play a role in regulating collagen synthesis in differentiated fibroblast. However, scx role in myocardial infarction (MI) and cardiac remodeling is unknown. Moreover, Angiotensin II (AngII) is a known mediator of collagen expression in MI. Therefore, it's interesting to examine the effects of AngII on scx using cardiac myofibroblasts (myoFb) isolated from the site of 28-day post-MI rat heart; these cells are implicated in adverse remodeling and fibrosis at the site of MI. In the present study, we used primary cultures of adult rat cardiac myoFb isolated from the site of 28-day post-MI heart and confluent myoFb were treated with (10−7 M) AngII, AngII + Losartan (AngII type 1 [AT1] receptor blocker) and an untreated control group. Our results from both western blot and qRT-PCR illustrated significant up regulation (p<0.05) of scx expression at gene and protein levels in the presence of AngII. Losartan treatment (1μM) abrogated the AngII induced expression of scx in cardiac myoFb in AngII + Losartan group. The data presented demonstrates that AngII effects are mediated by AT1 receptor and AngII modulates scx expression either directly or indirectly via TGF-β1.