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. Author manuscript; available in PMC: 2017 Mar 24.
Published in final edited form as: Cell. 2016 Mar 10;165(1):111–124. doi: 10.1016/j.cell.2016.02.011

Figure 7. Summary schemes illustrating gut-microbial involvement in development of platelet hyperresponsiveness and athero-thrombotic heart disease.

Figure 7

(A) Global schema illustrating metaorganismal pathway linking dietary sources of choline abundant in a Western diet, gut microbiota and host hepatic FMOs, resultant TMAO production, and subsequent development of hyperresponsive platelet phenotype and enhanced thrombotic event risk. Also shown are reported pro-atherosclerotic effects of TMAO and the potential involvement of TMAO in development of vulnerable plaque. EC, endothelial cell; FMOs, flavin monooxygenases; M[phage], macrophage; TMA, trimethylamine; TMAO trimethylamine N-oxide. (B) Chronic exposure to a diet rich in choline leads to a shift in the gut microbial composition and function, with consequent enhancement in host TMAO plasma levels. Platelet exposure to high levels of TMAO enhances sub-maximal stimulus (thrombin, ADP, collagen) evoked release of intracellular calcium stores, and platelet hyperresponsiveness. ADP, adenosine diphosphate; GPVI, glycoprotein VI; G<q>, G protein q; IP<3>, inositol 1,4,5-triphosphate; IP<3>R, Inositol 1,4,5-triphosphate receptor; P2Y12, purinergic receptor P2Y12; PAR, protease activated receptor; PLC, phospholipase C; PIP2, phosphatidylinositol 4,5-bisphosphate.