Blocking TLR2 activity diminishes and stabilizes advanced atherosclerotic lesions in apolipoprotein E-deficient mice

Abstract

The pharmacologic or genetic blockade of TLR2 activity diminishes and stabilizes advanced atherosclerotic lesions in ApoE(-/-) mice. Thus, targeting TLR2 signaling may be a promising therapeutic strategy against advanced atherosclerosis.

Vitamin K2 can suppress the expression of Toll-like receptor 2 (TLR2) and TLR4, and inhibit calcification of aortic intima in ApoE-/- mice as well as smooth muscle cells

“…8 On the other hand, blockade of TLR2 activity with the pharmacologic or genetic manipulations significantly reduced the plaque size, and increased plaque stability in the brachiocephalic arteries. 9 The protective effects of TLR2 antagonism were considered as associated with the suppression of the expression of pro-inflammatory cytokines IL-6 and TNF-a, and the inactivation of transcription factors NF-kB. Moreover, high-cholesterol diet more prominently accelerated atherosclerotic formation in ApoE -/mice.…”

The Anti-Inflammatory Effect of Taurine on Cardiovascular Disease

“…TLR2 and 4 have been shown to be atherogenic, while conflicting research regarding TLR9’s involvement in CVD pathologies has been shown in the literature [ 87 ]. TLR2-deficient mice susceptible to CVD and in vitro studies using human cells which investigated atherogenicity of TLR have shown that TLR2 plays a role in regulating ROS-induced endothelial and vascular inflammation [ 190 ], plaque formation [ 191 ], migration of vascular smooth muscle cells from the tunica media to the intima [ 192 ], and influences plaque stability [ 193 ]. Comparable results have been demonstrated in studies involving TLR4, as TLR4 has been associated with endothelial and vascular inflammation [ 194 , 195 ] and atherosclerotic plaque formation [ 196 ], and increases macrophage, foam cell, and lipid content of plaques [ 196 , 197 , 198 , 199 ], hypertension [ 200 ], plaque rupture [ 201 ], and migration of vascular smooth muscle cells [ 202 ].…”

Mechanisms of erosion of atherosclerotic plaques

“…7 Using ApoE −/− atherosclerotic mice, other groups found that TLR2 activation by exogenous ligands increases atherosclerotic plaque size and neointima formation in femoral arteries, notably through promoting ROS production and smooth muscle cell migration in an IL-6 dependent manner. 10–14 …”