Piezo1/ERK signaling pathway is activated in aortic VSMCs of patients with aortic dissection or aneurysm

Abstract

Abstract Background Piezo1 in vascular smooth muscle cells(VSMCs) is sensitive to the change of hemodynamic pressure and play the specific biological roles. ERK may be the key potential downstream signal of Piezo1. However, it remains unknown whether Piezo1/ERK signaling can be activated in aortic VSMCs of patients with aortic dissection(AD) or aneurysm(AA). Methods Piezo1 and p-ERK protein expressions were compared between AD/AA human aortic samples and normal samples by western blotting analysis and Immunohistochemistry. In addition, the rat thoracic VSMCs were divided into control, Yoda1( Piezo1 agonist), sch772984(ERK inhibitor) and Yoda1 + sch772984 groups. The cell life activities, including cell proliferation, migration, apoptosis, autophagy and phenotypical switch were measured. Results The patients with AD/AA had higher blood pressure than that of donors. We found that the expressions of Piezo1 and p-ERK in aortic media of AD/AA were higher than normal samples. In vitro experiments showed that Piezo1 could induce cell proliferation and migration by evoking ERK signaling, and this effect can be blocked by sch772984. Conclusions Piezo1/ERK signaling pathway is significantly activated in aortic VSMCs of patients with AD/AA, which might participate in AD/AA via promoting VSMCs proliferation and migration. This study provides a new insight into the biological action of Piezo1/ERK signaling pathway in the pathogenesis of AD/AA.