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

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.

• Authors: W Chen, H DU, G Qian, Y Zhou, Y Chen, Q Ma, X Wu, Y Sha
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 42 Issue 3 Pg. 330-337 (Mar 20 2022) ISSN: 1673-4254 [Print] China
• PMID: 35426795 (Publication Type: Journal Article)

Chemical References

• Apolipoproteins E
• Core Binding Factor Alpha 1 Subunit
• Membrane Proteins
• Tmbim6 protein, mouse
• bcl-2-Associated X Protein
• Caspase 3
• GTP Phosphohydrolases
• Opa1 protein, mouse
• Calcium

Topics

• Animals
• Apolipoproteins E (metabolism)
• Calcium (metabolism)
• Caspase 3 (metabolism)
• Cells, Cultured
• Core Binding Factor Alpha 1 Subunit (metabolism)
• Diabetes Mellitus, Experimental (metabolism, pathology)
• GTP Phosphohydrolases (biosynthesis, genetics, metabolism)
• Membrane Proteins (metabolism)
• Mice
• Mice, Knockout
• Muscle, Smooth, Vascular (metabolism, pathology)
• Myocytes, Smooth Muscle (metabolism, pathology)
• Optic Atrophy, Autosomal Dominant (metabolism, pathology)
• Osteogenesis
• Vascular Calcification (metabolism, pathology)
• bcl-2-Associated X Protein (metabolism)