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. Author manuscript; available in PMC: 2017 Feb 19.
Published in final edited form as: Circ Res. 2016 Feb 19;118(4):703–720. doi: 10.1161/CIRCRESAHA.115.306300

Figure 1. microRNA orchestration of cholesterol homeostasis and macrophage activation in atherosclerosis.

Figure 1

In the liver, miRNAs repress the expression of genes involved in lipoprotein packaging and secretion (eg. miR-30c, miR-27b), uptake (eg. miRNAs targeting LDLR and SRB1), and cholesterol efflux (eg. miRNA targeting ABCA1). miRNA repression of ABCA1 decreases cholesterol efflux to lipid-poor apolipoprotein A-I (apoA-I), and biogenesis of HDL. As the nascent HDL particle mediates free cholesterol (FC) uptake and remodels due to lecithin-cholesterol Acyltransferase (LCAT) conversion of FC to cholesterol ester (CE), secreted microRNAs, such as miR-223, miR-92a and miR-126 are detected on the mature HDL particles. These HDL carried and may mediate extracellular signaling by repressing genes in target tissues and HDL interaction with macrophages and endothelial cells may also result in miRNA exchange (ie. pick-up or delivery via scavenger receptor B1 (SR-B1). MiRNA targeting of SR-B1 and the ABC11 and ATP8B1 transporters reduce selective cholesterol uptake by the liver and excretion, respectively. In macrophages, miRNA targeting of ABCA1 reduces cholesterol efflux and reverse cholesterol transport back to the liver. In addition, miRNAs regulate the polarization of macrophages toward classical M1 (eg-33, miR-155) or alternative M2 (eg. miR-223, miR-27a) inflammatory activation, and also regulate lipoprotein uptake and foam cell formation. (Illustration Credit: Ben Smith).