| First Author | Guan H | Year | 2017 |
| Journal | J Am Heart Assoc | Volume | 6 |
| Issue | 2 | PubMed ID | 28209562 |
| Mgi Jnum | J:312844 | Mgi Id | MGI:6791740 |
| Doi | 10.1161/JAHA.116.004585 | Citation | Guan H, et al. (2017) Vinexin beta Ablation Inhibits Atherosclerosis in Apolipoprotein E-Deficient Mice by Inactivating the Akt-Nuclear Factor kappaB Inflammatory Axis. J Am Heart Assoc 6(2) |
| abstractText | BACKGROUND: Vinexin beta is a novel adaptor protein that regulates cellular adhesion, cytoskeletal reorganization, signal transduction, and transcription; however, the exact role that vinexin beta plays in atherosclerosis remains unknown. METHODS AND RESULTS: Immunoblot analysis showed that vinexin beta expression is upregulated in the atherosclerotic lesions of both patients with coronary heart disease and hyperlipemic apolipoprotein E-deficient mice and is primarily localized in macrophages indicated by immunofluorescence staining. The high-fat diet-induced double-knockout mice exhibited lower aortic plaque burdens than apolipoprotein E(-/-) littermates and decreased macrophage content. Vinexin beta deficiency improved plaque stability by attenuating lipid accumulation and increasing smooth muscle cell content and collagen. Moreover, the bone marrow transplant experiment demonstrated that vinexin beta deficiency exerts atheroprotective effects in hematopoietic cells. Consistent with these changes, the mRNA expression of proinflammatory cytokines were downregulated in vinexin beta(-/-) apolipoprotein E(-/-) mice, whereas the anti-inflammatory M2 macrophage markers were upregulated. The immunohistochemical staining and in vitro experiments showed that deficiency of vinexin beta inhibited the accumulation of monocytes and the migration of macrophages induced by tumor necrosis factor alpha-stimulated human umbilical vein endothelial cells as well as macrophage proliferation. Finally, the inhibitory effects exerted by vinexin beta deficiency on foam cell formation, nuclear factor kappaB activation, and inflammatory cytokine expression were largely reversed by constitutive Akt activation, whereas the increased expression of the nuclear factor kappaB subset promoted by adenoviral vinexin beta was dramatically suppressed by inhibition of AKT. CONCLUSIONS: Vinexin beta deficiency attenuates atherogenesis primarily by suppressing vascular inflammation and inactivating Akt-nuclear factor kappaB signaling. Our data suggest that vinexin beta could be a therapeutic target for the treatment of atherosclerosis. |
