Corylin Confers Vasoprotection via JDP2-Nrf2 Antioxidant Axis against Chronic Kidney Disease-Induced Smooth Muscle...

Vascular calcification is a pathological process involving vascular smooth muscle cells (VSMCs) phenotypic switching into osteoblast-like cells within a calcium phosphate-deposited environment. This transformation is a critical risk factor for cardiovascular morbidity and mortality in patients with hyperphosphatemia due to chronic kidney disease. Corylin, a major compound derived from the Chinese medicine herb Psoralea corylifolia, is beneficial for the cardiovascular system. However, its role in modulating VSMC phenotypic switching and calcification remains to be elucidated. A vascular calcification rat model induced by vitamin D3 plus nicotine (VDN) was established to evaluate the therapeutic effects of corylin. The protective effects of corylin were evaluated in high phosphate-induced vessels and VSMCs using cytotoxicity assay, Alizarin red S staining, alkaline phosphatase staining, immunofluorescence, Western blot analysis, and qPCR. The interaction between Jun dimerisation protein 2 (JDP2) and Nrf2 was analysed using a ChIP-qPCR assay. Corylin treatment ameliorated arteriosclerotic lesions and oxidative stress in rats treated with VDN. We also observed that the cytoprotective effects of corylin prevented VSMC apoptosis and deposition of calcium phosphates. Additionally, corylin decreased calcium overload by inhibiting calcineurin and maintaining mitochondrial homeostasis. We identified a robust co-induction of JDP2 and Nrf2 in corylin-treated VSMCs, which contributed to reducing phenotypic switching and abrogating oxidative stress. Furthermore, Nrf2 knockdown by an inhibitor abolished JDP2 activation and the protective effects of corylin. Our study reveals that corylin exerts anti-arteriosclerotic and vasculoprotective effects targeting JDP2-Nrf2 activation, making it a potential treatment for vascular calcification.