Mitoquinone attenuates vascular calcification by suppressing oxidative stress and reducing apoptosis of vascular smooth muscle cells via the Keap1/Nrf2 pathway.

Oxidative stress and apoptosis of vascular smooth muscle cells (VSMCs) are key to vascular calcification in patients with chronic kidney disease (CKD). The mitochondria-targeted antioxidant, mitoquinone (MitoQ), which reduces oxidative stress and apoptosis, has a protective effect in acute models of renal injury but whether MitoQ can attenuate vascular calcification in CKD patients is unknown. This study was conducted to investigate whether MitoQ can prevent calcification, both in vitro and in vivo. Adenine was used to induce calcification in rats, and inorganic phosphate was used to induce calcification in VSMCs. To elucidate the underlying molecular mechanism, a specific inhibitor of Nrf2, ML385, was used 1 h before MitoQ administration. Histological staining, ELISA, flow cytometry, alizarin red staining and western blotting were used to test this hypothesis. Administration of MitoQ alleviated calcification and oxidative stress. The anti-apoptotic effect of MitoQ was associated with upregulation of Bcl-2, downregulation of Bax, and increased Nrf2 expression. The effects of MitoQ were reversed by treatment with ML385. This study offers evidence that MitoQ attenuates vascular calcification by suppressing oxidative stress and apoptosis of VSMCs through the Keap1/Nrf2 pathway. MitoQ should be further investigated as a potential therapy to prevent vascular calcification in CKD patients.