HDL and microRNA therapeutics in cardiovascular disease.

microRNAs (miRNA) are small non-coding RNAs (sRNA) that post-transcriptionally regulate gene (mRNA) expression and are implicated in many biological processes and diseases. Many miRNAs have been reported to be altered in cardiovascular disease (CVD); both cellular and extracellular miRNA levels are affected by hypercholesterolemia and atherosclerosis. We and other groups have reported that lipoproteins transport miRNAs in circulation and these lipoprotein signatures are significantly altered in hypercholesterolemia and coronary artery disease (CAD). Extracellular miRNAs are a new class of potential biomarkers for CVD; however, they may also be new drug targets as high-density lipoproteins (HDL) transfer functional miRNAs to recipient cells in an endocrine-like form of intercellular communication that likely suppresses vascular inflammation. Recently, RNA-based drugs have emerged as the next frontier in drug therapy, and there are many miRNA inhibitors and mimics in clinical development. Here, we discuss specific miRNA drug targets and how their manipulation may impact CVD. We also address the potential for manipulating HDL-miRNA levels to treat CVD and the use of HDL as a delivery vehicle for RNA and chemical drugs. Finally, we outline the current and future challenges for HDL and miRNA-based therapeutics for the prevention and treatment of CVD.