A novel regulatory facet for hypertriglyceridemia: The role of microRNAs in the regulation of triglyceride-rich lipoprotein biosynthesis. (January 2023)

• Record Type: Journal Article
• Authors: Khalifeh, Masoumeh; Santos, Raul D.; Oskuee, Reza Kazemi; Badiee, Ali; Aghaee-Bakhtiari, Seyed Hamid; Sahebkar, Amirhossein
• Is Part Of: Progress in lipid research. Volume 89(2023)
• Publication Date: 2023-01
• Subjects: microRNAs -- Lipid metabolism -- Hypertriglyceridemia -- Triacylglycerol-rich lipoproteins -- Cardiovascular diseases; ACC Acetyl-CoA carboxylase -- AMPK AMP-activated protein kinase -- ANGPTL3 Angiopoietin-like protein 3 -- Apo B-48 Apolipoprotein B-48 -- Apo B100 Apolipoprotein B100 -- ApoC-III Apolipoprotein C-III -- ASCVD Atherosclerotic cardiovascular disease -- ASO Antisense oligonucleotide -- CVD Cardiovascular disease -- DGAT Acyl-CoA: Diacylglycerol acyltransferase -- DM Diabetes mellitus -- DNL De-novo lipogenesis -- EMA European Medicines Agency -- ER Endoplasmic reticulum -- FAS Fatty acid synthase -- FCS Familial chylomicronemia syndrome -- FDA Food and drug administration -- HDL-C HDL-cholesterol -- HDL High-density lipoprotein -- HMGCR 3-hydroxy-3-methylglutaryl-CoA reductase -- HTG Hypertriglyceridemia -- IDL Intermediate-density lipoprotein -- INSIG-2 Insulin-induced gene-2 -- IPE Icosapent ethyl -- LD Lipid droplet -- LDL Low-density lipoprotein -- LPL Lipoprotein lipase -- MGAT Acyl CoA: Monoacylglycerol acyltransferase -- miRNAs MicroRNAs, MTP -- mRNA messenger RNA, Microsomal triglyceride transfer protein -- NAFLD Non-alcoholic fatty liver disease -- NEFA Non-esterified fatty acid -- PCSK9 Proprotein convertase subtilisin/ Kexin type 9 -- SCD1 Stearoyl-CoA desaturase-1 -- SREBP Sterol response element-binding protein -- TAG triacylglycerol -- TAGRL Triacylglycerol-rich lipoproteins -- 3′-UTR 3′-untranslated region, -- VLDL Very-low density lipoprotein; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2022.101197
• Languages: English
• ISSNs: 0163-7827

Abstract

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.