The role of TRPV1 channels in atherosclerosis

Figures

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  Figure 1.. The formation of atherosclerosis. During atherosclerosis, LDL-C enters the endangium through damaged endothelial cells and is oxidized to ox-LDL-C. Macrophages enter the endangium under the action of adhesion factors and chemokines, and VSMCs proliferate and migrate from the membrane to the intima. The scavenger receptor (SR) of macrophages and VSMCs recognizes and devours ox-LDL-C to form foam cells that form early lipid streaks.

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  Figure 2.. Effect of TRPV1 on the proliferation of VSMCs and the formation of smooth muscle cell-derived foam cells. Activation of TRPV1 channels in smooth muscle cells can increase Ca2+ inflow, increase the expression of ATP binding box transporter A1 (ABCA1, cholesterol efflux regulatory protein) and reduce the expression of low-density lipoprotein-related protein 1 (LRP 1, cholesterol inflow regulator protein) through CaM- and PKA-dependent mechanisms to promote the outflow of LDL and reduce VSMC lipid storage. It can also activate the autophagy-lysosomal pathway of VSMCs through the AMPK signaling pathway to recover autophagy damage by ox-LDL and ultimately inhibit the formation of foam cells. In addition, activation of TRPV1 can inhibit the proliferation of VSMCs through the cAMP/PKA pathway, and NO can enhance this effect by increasing the cAMP level. TRPV1 activation can inhibit the proliferation and migration of VSMCs by activating the antigrowth adenosine 5ʹ-monophosphate-activated protein kinase (AMPK) signaling pathway. It can also inhibit the Ang II-induced proliferation and migration of VSMCs by deactivating the epidermal growth factor receptor (EGFR)-ERK 1/2 pathway.

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  Figure 3.. Effect of TRPV1 channels on the protection of ECs and the formation of macrophage-derived foam cells. Activation of TRPV1 channels in endothelial cells can increase intracellular Ca2+ levels and promote PKA, CaMKII and AMPK activation. PKA and AMPK can promote eNOS phosphorylation and increase the level of NO, which can promote vasodilation and angiogenesis. Activation of PKA can upregulate uncoupling protein 2 (UCP2) expression, reduce ROS production, increase resistance to oxidative stress, and reduce endotheliocyte damage, foam cell formation and atherosclerosis. In addition, activation of TRPV1 channels can activate the Ca2+-dependent phosphatidylinositol 3 kinase (PI3K)/Akt pathway to inhibit the activation of NF-B, which can inhibit cytokines, chemokines, adhesion factors and monocyte adhesion to inhibit the inflammatory response of ECs.