**3.4 MicroRNAs (miRNAs) in HDL**

miRNAs are small noncoding RNAs that suppress gene expression through posttranscriptional regulation of mRNA stability. Extracellular miRNAs likely serve as the cellular messages, which are transported between cells in an endocrine form of intercellular communication via circulation. In the blood vessels, these transferring miRNAs modulate atherosclerosis and angiogenesis, and in the heart, they modulate ischemic/reperfusion (I/R) injuries, myocardial infarction, and heart failure. In plasma, they are protected from circulating ribonucleases through the association with lipoproteins [64]. Especially, HDL is reported to be the major carrier of miR-NAs in plasma. Furthermore, HDL exhibits an independent miRNA profile distinct from that of plasma through the micro-transcriptome assay, which might notably influence the biological functions of HDL [65].

HDL transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Cellular export of miRNAs to HDL is regulated by neutral sphingomyelinase. Injecting reconstituted HDL (rHDL) into mice retrieves distinct miRNA profiles from normal and atherogenic animal models. Furthermore, HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be dependent on SR-BI. The human HDL-miRNA profiles in healthy subjects are significantly different from those of familial hypercholesterolemia subjects. Notably, HDL-miRNAs from atherosclerotic subjects induce differential gene expression [66, 67]. Collectively, these observations indicated that HDL participates in a mechanism of intercellular communication through the delivery of miRNAs.

Some studies reported that the contents of miR-486 and miR-92a in HDL are reduced in vulnerable CVD patients [68]. HDL-associated miR-223 levels are decreased after high-protein diet-induced weight loss in overweight and obese males [69]. Intestinal lymphatic HDL-associated miR-223 is reduced during insulin resistance and is restored by niacin in rats [70]. Furthermore, HDL-transferred miR-223 inhibits intercellular adhesion molecule-1 (ICAM-1) expression in endothelial cells [71].
