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

Prog Lipid Res. 2023 Jan:89:101197. doi: 10.1016/j.plipres.2022.101197. Epub 2022 Nov 15.

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. MiRNA-based 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.

Keywords: Cardiovascular diseases; Hypertriglyceridemia; Lipid metabolism; Triacylglycerol-rich lipoproteins; microRNAs.

Publication types

  • Review

MeSH terms

  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors* / therapeutic use
  • Hypertriglyceridemia* / drug therapy
  • Hypertriglyceridemia* / therapy
  • Lipoproteins / genetics
  • Lipoproteins / metabolism
  • Lipoproteins / therapeutic use
  • MicroRNAs* / genetics
  • Triglycerides / metabolism

Substances

  • MicroRNAs
  • Triglycerides
  • Lipoproteins
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors