Modulation of the Cellular microRNA Landscape: Contribution to the Protective Effects of High-Density Lipoproteins (HDL)

SIMPLE SUMMARY: High-density lipoproteins are often described as the ‘good’ cholesterol in the bloodstream, as this complex of lipids (fats) and proteins is known to protect many cells and tissues against damage. One aspect of this protective function may be the ability of this lipoprotein class to modify the expression of small pieces of RNA (microRNA) which can regulate the expression of networks of genes which encode proteins that mediate cellular functions. Understanding the sequences involved in sustaining cellular function may provide a novel route to new therapeutics. ABSTRACT: High-density lipoproteins (HDL) play an established role in protecting against cellular dysfunction in a variety of different disease contexts; however, harnessing this therapeutic potential has proved challenging due to the heterogeneous and relative instability of this lipoprotein and its variable cargo molecules. The purpose of this study is to examine the contribution of microRNA (miRNA; miR) sequences, either delivered directly or modulated endogenously, to these protective functions. This narrative review introduces the complex cargo carried by HDL, the protective functions associated with this lipoprotein, and the factors governing biogenesis, export and the uptake of microRNA. The possible mechanisms by which HDL can modulate the cellular miRNA landscape are considered, and the impact of key sequences modified by HDL is explored in diseases such as inflammation and immunity, wound healing, angiogenesis, dyslipidaemia, atherosclerosis and coronary heart disease, potentially offering new routes for therapeutic intervention.