A big role for small RNAs in HDL homeostasis

Mireille Ouimet; Kathryn J. Moore

doi:10.1194/jlr.R036327

A big role for small RNAs in HDL homeostasis

Mireille Ouimet and
Kathryn J. Moore¹

Departments of Medicine and Cell Biology, Marc and Ruti Bell Vascular Biology and Disease Program, Leon H. Charney Division of Cardiology, New York University School of Medicine, New York, NY 10016

Abstract

High-density lipoproteins play a central role in systemic cholesterol homeostasis by stimulating the efflux of excess cellular cholesterol and transporting it to the liver for biliary excretion. HDL has long been touted as the “good cholesterol” because of the strong inverse correlation of plasma HDL cholesterol levels with coronary heart disease. However, the disappointing outcomes of recent clinical trials involving therapeutic elevations of HDL cholesterol have called this moniker into question and revealed our lack of understanding of this complex lipoprotein. At the same time, the discovery of microRNAs (miRNAs) that regulate HDL biogenesis and function have led to a surge in our understanding of the posttranscriptional mechanisms regulating plasma levels of HDL. Furthermore, HDL has recently been shown to selectively transport miRNAs and thereby facilitate cellular communication by shuttling these potent gene regulators to distal tissues. Finally, that miRNA cargo carried by HDL may be altered during disease states further broadened our perspective of how this lipoprotein can have complex effects on target cells and tissues. The unraveling of how these tiny RNAs govern HDL metabolism and contribute to its actions promises to reveal new therapeutic strategies to optimize cardiovascular health.

Footnotes

↵1 To whom correspondence should be addressed. e-mail: Kathryn.Moore{at}nyumc.org
Abbreviations:

ARL7

ADP-ribosylation factor-like 7

CETP

cholesteryl ester transfer protein

CVD

cardiovascular disease

EFNA1

ephrin A1

FH

familial hypercholesterolemia

HDL-C

HDL-cholesterol

LDLR

LDL receptor

LNA

locked nucleic acid

LXR

liver X receptor

miRNA

microRNA

pre-miRNA

precursor microRNA

pri-miRNA

primary microRNA

RCT

reverse cholesterol transport

SR-BI

scavenger receptor class B, type I
Research on microRNAs in the Moore Lab is supported by National Institutes of Health Grant R01 HL-108182, and M.O. is supported by a postdoctoral fellowship from the Canadian Institutes of Health Research. K.J.M. is a member of the miR-33 Clinical Advisory Board of Regulus Therapeutics.