Tadalafil Attenuates Angiotensin II-Induced Extracellular Matrix Remodeling in Cardiac Fibroblasts Through TGF-β1/Smad3 Signaling Pathway

Cardiac fibrosis is a common consequence of various cardiac diseases and is linked to the activation of cardiac fibroblasts (FBs). This study aimed to investigate the effect of tadalafil (Tad) on cardiac fibrosis by regulating FB transformation and its molecular mechanism. Angiotensin II (Ang II) treated FBs were used to construct in vitro cardiac fibrosis models. FBs were divided into three groups: control, Ang II, and Ang II+ Tad. Immunofluorescence, real-time quantitative PCR, Western blot, and flow cytometry were utilized to detect the expression of alpha-SMA, collagen types I and III, fibronectin, Bcl-2, Bax, Bad, TGF-beta 1, SMAD3, p-SMAD3, and apoptosis. The expression of alpha-SMA, collagen types I and III, fibronectin, and Bcl-2 in the Ang II+ Tad group was significantly decreased, while the expressions of Bax and Bad were increased compared to the Ang II group. The Ang II+ Tad group also had the highest proportion of apoptosis. The TGF-beta 1/Smad3 signaling pathway was found to be inhibited in the Ang II+ Tad group. Therefore, Tad can inhibit Ang II-induced FB activation through the TGF-beta 1/Smad3 pathway and promote apoptosis of activated FBs.

Automated summary

This study found that tadalafil can inhibit cardiac fibrosis induced by angiotensin II by regulating the TGF-beta 1/Smad3 signaling pathway and promoting apoptosis of cardiac fibroblasts.