Renin and (pro)renin receptor induced vascular smooth muscle cell proliferation and neointimal hyperplasia by activating oxidative stress and inflammation

Background Numerous studies have shown that the proliferation and migration of vascular smooth muscle cells (VSMCs) were the pathological basis of restenosis occurrence. And Renin and prorenin could promote the proliferation of VSMCs through (pro)renin receptor ((P)RR). Therefore, this study aimed to observe the role of (P)RR in the proliferation of VSMCs in vitro and neointimal hyperplasia in the arterial injury model. Methods Cell proliferation was measured by CCK-8 and flow cytometry; RT-PCR and WB assays were used to detect the expressions of cyclin D1, PCNA, (P)RR, NOX1, and PI3K/AKT signal proteins; immunofluorescent staining was conducted to measure the expression of (P)RR; the levels of renin, PDGF-BB, inflammatory factors, and oxidative stress were determined by ELISA; pathological change was observed by HE staining. Results In this study, we demonstrated that renin could promote the proliferation of rat VSMCs by enhanced cell viability and cell cycle proteins, but silencing (P)RR restrained this. Then, we found that renin could enhance the levels of NOX1-mediated oxidative stress and inflammation by activating ERK1/2-AKT pathway in vitro. Similarly, inhibition of (P)RR resulted in opposite phenomenon. Importantly, inhibition of (P)RR could inhibit the neointimal hyperplasia in vivo after common carotid artery injury through restraining NOX1-mediated oxidative stress by down-regulating ERK1/2-AKT pathway. Conclusion We concluded that renin and (P)RR induced vascular smooth muscle cell proliferation and neointimal hyperplasia by activating oxidative stress, inflammation and ERK1/2-AKT pathway in an angiotensin Ⅱ (Ang Ⅱ)-independent manner.