The role of Angiotensin type 1 receptor and Src kinase in stretch induced cardiac fibroblast injury model

Abstract

Cardiac hypertrophy is a central risk factor of cardiac morbidity and mortality. Mechanical stretch activated Angiotensin II type I (AT1) receptor without the involvement of Angiotensin II (AngII) during the development of cardiac hypertrophy and causes secretion of Ang II, which plays a central role in mechanical stretch-induced hypertrophy. Here, we attempted to show the role of AT1 receptor and Src kinase in mechanical stretch-induced cardiac fibroblasts injury. Western blot analysis showed the differentiation of stimulation by Ang II and mechanical stretch triggered ERK1/2 phosphorylation was suppressed by Losartan, Src phosphorylation was suppressed by AZD0530 or both inhibitors on Akt phosphorylation. The phosphorylation of ERK and Src were increased by Ang II (100nM) and by mechanical stretch in 1hour. The effect of Ang II and stretch on ERK was blocked by Losartan and Src phosphorylation was suppressed by AZD0530.However, both Losartan and AZD0530 did not effect on Akt phosphorylation induced by Ang II, but they are could inhibit in stretch-induced Akt phosphorylation. We investigated that Losartan and AZD0530 can be took part in effect of mechanical stretch and Ang II induced cardiac fibroblast dysfunction. Moreover, mechanical stretch and Ang II induced all of three kinases phosphorylation that involves AT1 receptor. But they are might be located in different pathways.