Vinexin β Ablation Inhibits Atherosclerosis in Apolipoprotein E–Deficient Mice by Inactivating the Akt–Nuclear Factor κB Inflammatory Axis

Abstract

BackgroundVinexin β is a novel adaptor protein that regulates cellular adhesion, cytoskeletal reorganization, signal transduction, and transcription; however, the exact role that vinexin β plays in atherosclerosis remains unknown.Methods and ResultsImmunoblot analysis showed that vinexin β 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 β 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 β deficiency exerts atheroprotective effects in hematopoietic cells. Consistent with these changes, the mRNA expression of proinflammatory cytokines were downregulated in vinexin β−/− apolipoprotein E−/− mice, whereas the anti‐inflammatory M2 macrophage markers were upregulated. The immunohistochemical staining and in vitro experiments showed that deficiency of vinexin β inhibited the accumulation of monocytes and the migration of macrophages induced by tumor necrosis factor α–stimulated human umbilical vein endothelial cells as well as macrophage proliferation. Finally, the inhibitory effects exerted by vinexin β deficiency on foam cell formation, nuclear factor κB activation, and inflammatory cytokine expression were largely reversed by constitutive Akt activation, whereas the increased expression of the nuclear factor κB subset promoted by adenoviral vinexin β was dramatically suppressed by inhibition of AKT.ConclusionsVinexin β deficiency attenuates atherogenesis primarily by suppressing vascular inflammation and inactivating Akt–nuclear factor κB signaling. Our data suggest that vinexin β could be a therapeutic target for the treatment of atherosclerosis.

[Retracted] MIP‐1α Level and Its Correlation with the Risk of Left Atrial Remodeling in Patients with Atrial Fibrillation

“…In recent years, with the deepening of the research, the MIP-1 α effect on the tumor microenvironment has gradually transferred to cardiovascular diseases. MIP-1 α can be utilized to predict clinical outcomes in patients with atherosclerotic cardiovascular disease, myocardial ischemia, and heart failure [ 13 ]. In cardiac-specific transgenic mice [ 14 ], the CCR9 and CCL3 overexpression enhanced pressure overload-induced cardiac hypertrophy; CCL3 and CCL4 levels were higher in the hearts of transverse aortic stenosis mice compared with sham-operated mice.…”

Genome-wide association studies for immunoglobulin concentrations in colostrum and serum in Chinese Holstein

“…SORBS3 encodes an SH3 domain-containing adaptor protein that regulates cell adhesion and signal transduction. The deficiency of adaptor protein could suppress vascular inflammation and inactivate Akt–nuclear factor κB signaling [ 32 ]. IGHV1S18 is an immunoglobulin heavy chain variable region that encodes Ig heavy chain and is directly related to the formation of immunoglobulins.…”

Myotubularin-related protein 14 suppresses cardiac hypertrophy by inhibiting Akt

“…Next, to further assess the molecular mechanisms underlying the effects of MTMR14, we tested the downstream pathways involved in MTMR14-mediated CH pathogenesis. Since the Akt signaling pathway has emerged as an essential intracellular pathway in CH, particularly AKT/GSK3β/mTOR pathways as regulators of CH [15][16][17] , we first studied the potential involvement of Akt signaling pathways in the pro-hypertrophic role of MTMR14. The Western blotting results showed that the phosphorylation levels of Akt, GSK3β, mTOR, and p70-S6K were significantly increased in hypertrophic hearts in MTMR14-CKO mice compared with the hearts of MTMR14-Flox controls subjected to AB surgery (Fig.…”