PTPRE Exacerbates Phenotypic Transformation of Vascular Smooth Muscle Cells and Vasomotor Dysfunction in Salt‐Sensitive Hypertension

Prior studies have identified atypical expression of protein tyrosine phosphatase receptor type E (PTPRE) in animal models of salt-sensitive hypertension (SSH). This study investigates PTPRE's role in SSH and clarifies its mechanism of action. Through gene knockdown and overexpression of PTPRE in DOCA-salt hypertensive mice, we assessed the vasomotor function of aortic rings. PTPRE-induced phenotypic changes in vascular smooth muscle cells (VSMCs) were identified using phenotypic markers and related functional parameters. The phosphorylation levels of the MAPK signaling pathway subfamilies were assessed using Western blot analysis. Upregulation of PTPRE was observed in the VSMCs of DOCA-salt-induced SSH mice. This upregulation was associated with impaired vasoconstriction and vasodilation of arteries, as well as increased blood pressure (BP) (all p < 0.01). Altering PTPRE expression via knockdown and overexpression markedly affected the expression of synthetic (OPN) and contractile (α-SMA and SM22α) phenotype markers in the aortic media and VSMCs of SSH mice (all p < 0.01). Moreover, PTPRE expression influenced the phosphorylation activation within the MAPK signaling pathway. Specifically, regulation of PTPRE expression in SSH modulated the phosphorylation of the JNK and p38 MAPK subfamilies, along with the upstream phosphorylation of MKK3 and MKK6 (all p < 0.05). Our findings indicate that PTPRE significantly contributes to vascular vasomotor dysfunction and the phenotypic transformation of VSMCs in SSH. This involvement in SSH development seems to occur mainly via modulation of the JNK and p38 MAPK pathways.