Figure. miRNA regulation of HDL-C metabolism.

ABCA1, a major transporter that regulates HDL biogenesis and cholesterol efflux in macrophages accumulated in the artery wall, is regulated by a number of miRNAs including miR-33. miR-33 controls numerous steps of the reverse cholesterol transport pathway by regulating the expression of numerous genes associated with HDL biogenesis (ABCA1), cholesterol efflux in peripheral tissues including macrophages and cardiac fibroblasts [ABCA1 and ABCG1 (only in rodents)] and bile acid synthesis (CYP7A1) and secretion (ABCB11 and ATP8B1)in liver. In addition, miR-33 also promotes lipid accumulation in macrophages and favors Mtb survival by targeting the expression of key autophagy effectors ATG5, ATG7, ATG12, LAMP-1 and LIPA and controls macrophage polarization by regulating the expression of PRKAA1, AMPK and ALDH1A2. In addition to miR-33, ABCA1 is highly regulated at the post-transcriptional level in several tissues by numerous miRNAs including miR-148a, miR-144, miR-101, miR-128, miR-27a/b, miR-302a and miR-10b. Free cholesterol in nascent HDL is further esterified to cholesteryl esters by lecithin-cholesterol acyltransferase (LCAT) leading to the formation of mature HDL particles. HDL particles deliver cholesterol to the liver via the SRB1 receptor, which is also regulated by several miRNAs including miR-185, miR-223, and miR-96. This figure was performed using the Servier Medical Art illustration resources.