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. 2019 Nov 19;10:1360. doi: 10.3389/fphar.2019.01360

Figure 1.

Figure 1

TMAO-involved mechanisms promoting AS. (A) TMAO and inflammation-immunity. In this mechanism, elevated TMAO activates the expression of SR-A1 and CD36 in macrophages, thus stimulating the uptake of ox-LDL and foam cell formation; the TMAO-induced increase in HSP expression is also involved in this process. TMAO levels are positively associated with monocyte activation and inflammation. Elevated TMAO levels also induce NLRP3 inflammasome activation and subsequently trigger inflammatory and immune responses. (B) TMAO and inflammation. Elevated TMAO levels lead to inflammation, accompanied with increased expression of pro-inflammatory cytokines and decreased expression of anti-inflammatory cytokines. (C, D) TMAO also inhibits bile acid synthesis and RCT, contributes to platelet hyperreactivity, and enhances the potential for thrombosis; all of which promote the occurrence of AS. AS, atherosclerosis; HSP, heat shock protein; RCT, reverse cholesterol transport; FXR, farnesoid X receptor; SHP, small heterodimer partner; Npc1L1, Niemann-Pick C1-like1; CRP, C-reactive protein; FMO3-KO, FMO-3 knockout; TF, tissue factor; VCAM-1, vascular cell adhesion molecule-1; JNK, c-JUN NH2-terminal protein kinase; ERK, extracellular signal-regulated kinase.