The effect of mechanical stretch on cardiac fibroblast

Abstract

Hypertrophy results in cardiac infarction that makes higher fatality. There are many causes inducing hypertrophy. One of reasons is high blood pressure that lets mechanical stretch apply to a heart. Mechanical stretch could lead to hypertrophy. The markers of hypertrophy are characterized by differentiation of fibroblast to myofibroblast and extracellular matrix (ECM) formation. Angiotensin Ⅱ (Ang Ⅱ) is a vasoactive hormone and a strong agent that initiates hypertrophic response and myofibroblast formation. Losartan is an angiotensin Ⅱ type 1 receptor (AT1R) blocker that makes AT1R not work. Transforming Growth Factor-β1 (TGF-β1) is another activator that triggers differentiation inhibited by SB431542. So the present study investigated that mechanical stretch causing hypertension could be blocked by Losartan and SB431542. AT1R existed in cardiac fibroblasts and it was activated by Ang Ⅱ in proportion to Ang Ⅱ concentration. pERK, one of crucial signaling cascades for Ang Ⅱ activation, could be attenuated by Losartan. However, the phosphorylation of ERK under mechanical stretch was not diminished by Losartan. Interestingly, pSmad2, one of downstream of TGF-β1 pathway is always activated and mechanical stretch downregulates the expression of pSmad2. Also SB431542, blocker of TGF-β1 receptor, could not block pERK activation under mechanical stretch. Taken together, pERK activation induced by mechanical stretch could not be reduced by Losartan and SB431542, and mechanical stretch doesn't activate TGF-β1 receptor on cardiac fibroblasts. From these results, even if AT1R is blocked by Losartan, the pERK doesn't attenuate in cardiac fibroblasts, and the stretch doesn't prompt differentiation of cardiac fibroblasts through TGF-β1 receptors.