Journal of Southern Medical University

Journal of Southern Medical University ›› 2022, Vol. 42 ›› Issue (3): 330-337.doi: 10.12122/j.issn.1673-4254.2022.03.03

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Bax inhibitor 1 inhibits vascular calcification in mice by activating optic atrophy 1 expression

CHEN Weiren, DU Hui, QIAN Geng, ZHOU Yujie, CHEN Yundai, MA Qian, WU Xueping, SHA Yuan   

  1. Department of Cardiology, Beijing Anzhen Hospital of Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease; Department of Cardiology, Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital; Department of Cardiology, First Medical Center, Chinese PLA General Hospital
  • Online:2022-03-20 Published:2022-04-11

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Abstract: Objective To investigate the effects of Bax inhibitor 1 (BI- 1) and optic atrophy protein 1 (OPA1) on vascular calcification (VC). Methods Mouse models of VC were established in ApoE-deficient (ApoE-/-) diabetic mice by high-fat diet feeding for 12 weeks followed by intraperitoneal injections with Nε-carboxymethyl-lysine for 16 weeks. ApoE-/- mice (control group), ApoE-/- diabetic mice (VC group), ApoE-/- diabetic mice with BI-1 overexpression (VC + BI-1TG group), and ApoE-/-diabetic mice with BI-1 overexpression and OPA1 knockout (VC+BI-1TG+OPA1-/- group) were obtained for examination of the degree of aortic calcification using von Kossa staining. The changes in calcium content in the aorta were analyzed using ELISA. The expressions of Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP-2) were detected using immunohistochemistry, and the expression of cleaved caspase-3 was determined using Western blotting. Cultured mouse aortic smooth muscle cells were treated with 10 mmol/L β-glycerophosphate for 14 days to induce calcification, and the changes in BI-1 and OPA1 protein expressions were examined using Western blotting and cell apoptosis was detected using TUNEL staining. Results ApoE-/- mice with VC showed significantly decreased expressions of BI-1 and OPA1 proteins in the aorta (P=0.0044) with obviously increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P=0.0041). Overexpression of BI-1 significantly promoted OPA1 protein expression and reduced calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P=0.0006). OPA1 knockdown significantly increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 in the aorta (P=0.0007). Conclusion BI-1 inhibits VC possibly by promoting the expression of OPA1, reducing calcium deposition and inhibiting osteogenic differentiation and apoptosis of the vascular smooth muscle cells.

Key words: Bax inhibitor 1; optic atrophy protein 1; vascular calcification; osteogenic differentiation; apoptosis