A novel regulatory facet for hypertriglyceridemia: The role of microRNAs in the regulation of triglyceride-rich lipoprotein biosynthesis

Abstract

Atherosclerotic cardiovascular disease (ASCVD) is one of the major leading global causes of death. Genetic and epidemiological studies strongly support the causal association between triacylglycerol-rich lipoproteins (TAGRL) and atherogenesis, even in statin-treated patients. Recent genetic evidence has clarified that variants in several key genes implicated in TAGRL metabolism are strongly linked to the increased ASCVD risk. There are several triacylglycerol-lowering agents; however, new therapeutic options are in development, among which are miRNA-based therapeutic approaches. MicroRNAs (miRNAs) are small non-coding RNAs (18-25 nucleotides) that negatively modulate gene expression through translational repression or degradation of target mRNAs, thereby reducing the levels of functional genes. MiRNAs play a crucial role in the development of hypertriglyceridemia as several miRNAs are dysregulated in both synthesis and clearance of TAGRL particles. MiRNAbased therapies in ASCVD have not yet been applied in human trials but are attractive. This review provides a concise overview of current interventions for hypertriglyceridemia and the development of novel miRNA and siRNA-based drugs. We summarize the miRNAs involved in the regulation of key genes in the TAGRLs synthesis pathway, which has gained attention as a novel target for therapeutic applications in CVD.