Fig. 7

Effect of thrombin on smooth muscle cells(SMCs) in the pathogenesis of atherosclerosis. Thrombin induces the synthesis of pro-inflammatory cytokines and chemokines in SMCs, including IL6, IL8/CXCL8, IL33, CCl2/ MCP-1, IL11, and PTGS2, which in turn induces monocytes and neutrophil migration and adhesion to inflammatory sites. Thrombin promotes SMCs proliferation and angiogenesis in atherosclerotic plaque. LDL intake by scavenger receptor (SR) is delivered to the lysosome (LY), where it is hydrolyzed to free cholesterol before entering the endoplasmic reticulum(ER). Subsequently, lipid droplets(LDs) rich in cholesterol esters(CEs) are formed from the ER. There are two pathways of LD lipolysis: 1. Lipase-mediated intracytoplasmic hydrolysis of LD-associated neutral lipids; 2. Autophagosome mediates the cytoplasmic transport of LD to the lysosome, where LD cholesterol ester is hydrolyzed by lysosomal acid lipase. Thrombin may inhibit both pathways. Eventually, free cholesterol is excreted from the cell by ABCA1