Deficiency of TDAG51 Protects Against Atherosclerosis by Modulating Apoptosis, Cholesterol Efflux, and Peroxiredoxin‐1 Expression

摘要: Background Apoptosis caused by endoplasmic reticulum (ER) stress contributes to atherothrombosis, the underlying cause of cardiovascular disease (CVD). T-cell death-associated gene 51 (TDAG51), a member pleckstrin homology-like domain family, is induced ER stress, causes apoptosis when overexpressed, and present in lesion-resident macrophages endothelial cells. Methods Results To study role TDAG51 atherosclerosis, male mice deficient apolipoprotein E ( −/− / ApoE ) were generated showed reduced atherosclerotic lesion growth (56±5% reduction at 40 weeks, relative controls, P <0.005) necrosis (41±4% versus 63±8% area /ApoE , respectively; <0.05) without changes plasma levels lipids, glucose, inflammatory cytokines. deficiency several phenotypic cells that increase cytoprotection against oxidative enhance PPARγ-dependent reverse cholesterol transport, upregulate peroxiredoxin-1 (Prdx-1), an antioxidant enzyme with antiatherogenic properties (1.8±0.1-fold Prdx-1 protein expression, control macrophages; <0.005). Two independent case–control studies found genetic variant human region (rs2367446) associated CVD (OR, 1.15; 95% CI, 1.07 1.24; =0.0003). Conclusions These findings provide evidence affects specific cellular pathways known reduce atherogenesis, suggesting modulation expression or its activity may have therapeutic benefit for treatment CVD.