Lovastatin attenuates angiotensin II induced cardiovascular fibrosis through the suppression of YAP/TAZ signaling.

Lovastatin attenuates angiotensin II induced cardiovascular fibrosis through the suppression of YAP/TAZ signaling. Biochem Biophys Res Commun. 2019 Mar 26;: Authors: Wu P, Liu Z, Zhao T, Xia F, Gong L, Zheng Z, Chen Z, Yang T, Duan Q Abstract Angiotensin II (ANG II) is associated with fibrosis in both clinical and basic studies. Thus, we aimed to explore a mechanism by which ANG II induces fibrosis. 5 μM of ANG II was used in the in vitro study. The mouse cardiovascular fibrosis model was established by infused with AngII (1000 ng/kg/min) for 7 days and cotreated with lovastatin (10 mg/kg daily) or vehicle control (DMSO in saline). We found that ANG II activated yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), two transcription factors that were shown to induce fibrosis. Inhibition of ras homolog gene family member A (RhoA) reduced ANG II-induced YAP/TAZ transcriptional activity, which suggests that the upregulation of YAP/TAZ signaling by ANG II is RhoA-dependent. Furthermore, studies have shown that the inhibition of YAP/TAZ by either siRNA or small molecule inhibitor suppressed ANG II-induced expression of fibrogenic genes, indicating that ANG II upregulates YAP/TAZ to initiate fibrosis. The mevalonate pathway, which is targeted by statins, has also been shown to control YAP/TAZ. Here, we found that the suppression of YAP/TAZ signaling by lovastatin attenuates ANG II-induced fibros...
Source: Biochemical and Biophysical Research communications - Category: Biochemistry Authors: Tags: Biochem Biophys Res Commun Source Type: research