Figure 3. Mechanism of matrix stiffness-induced cardiac myofibroblast differentiation.

Upregulation and activation of AT₁R induced by stiff substrate enhanced cardiac myofibroblast differentiation. (a) A significantly (p < 0.05) higher gene expression level of AT₁R was observed in cardiac fibroblasts cultured on 30 kPa substrates and cell culture plate (^*p < 0.05 relative to 4 kPa; ^#p < 0.05 relative to 13 kPa; ⁺p < 0.05 relative to 30 kPa). Fold change was expressed relative to 4 kPa substrates. (b) The α-SMA in cardiac fibroblasts cultured on 30 kPa and cell culture plate appeared to be reduced in the presence of losartan (AT₁R inhibitor). Scale bar: 50 μm. (c) Losartan significantly (p < 0.05) lowered gene expression levels of α-SMA, TGF-β1, Col I and Col III in cardiac fibroblasts cultured on 30 kPa substrates and cell culture plate (*p < 0.05 relative to -losartan). Fold change was expressed in relative to 4 kPa substrates with – losartan.