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Published on: January 16, 2018
Non-coding RNAs in lipid metabolism
Xinbo Zhang1, Nathan L Price1, Carlos Fernández-Hernando1
1Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Department of Pathology, Yale University School of Medicine, 10 Amistad St., New Haven, CT 06510. USA.
Insights
Non-coding RNAs, including microRNAs (miRNAs) and long-non-coding RNAs (lncRNAs), are key regulators of lipid metabolism. Understanding their role in cardiovascular disease (CVD) offers new therapeutic strategies.
Area of Science:
- Molecular Biology
- Genetics
- Cardiology
Background:
- Cardiovascular disease (CVD) is a leading cause of death, initiated by lipid accumulation in arteries (atherogenesis).
- Dysregulation of lipid metabolism significantly increases cardiometabolic disorder risk.
- Current CVD prevention primarily focuses on managing lipid disorders.
Purpose of the Study:
- To review the critical roles of microRNAs (miRNAs) and long-non-coding RNAs (lncRNAs) in regulating lipid metabolism.
- To explore the implications of these non-coding RNAs in cardiovascular disease (CVD) pathogenesis.
- To discuss their potential as therapeutic targets for CVD treatment.
Main Methods:
- Literature review of studies on non-coding RNAs, lipid metabolism, and CVD.
- Analysis of research on specific miRNAs (e.g., miR-33, miR-122, miR-148a) and lncRNAs.
- Synthesis of findings on post-transcriptional gene regulation in lipid homeostasis.
Main Results:
- miRNAs like miR-33, miR-122, and miR-148a are established regulators of cholesterol homeostasis and lipoprotein metabolism.
- lncRNAs are emerging as significant, albeit less understood, regulators of lipid and lipoprotein metabolism.
- These non-coding RNAs primarily exert their influence at the post-transcriptional level.
Conclusions:
- Non-coding RNAs, particularly miRNAs, play crucial roles in lipid metabolism and CVD development.
- Further research is needed to fully elucidate the functions of lncRNAs in lipid metabolism and CVD due to their complexity and interspecies variability.
- Targeting miRNAs and lncRNAs presents a promising avenue for novel CVD therapies.
Abstract:
Cardiovascular disease (CVD), the leading cause of death and morbidity in the Western world, begins with lipid accumulation in the arterial wall, which is the initial step in atherogenesis. Alterations in lipid metabolism result in increased risk of cardiometabolic disorders, and treatment of lipid disorders remains the most common strategy aimed at reducing the incidence of CVD. Work done over the past decade has identified numerous classes of non-coding RNA molecules including microRNAs (miRNAs) and long-non-coding RNAs (lncRNAs) as critical regulators of gene expression involved in lipid metabolism and CVD, mostly acting at post-transcriptional level. A number of miRNAs, including miR-33, miR-122 and miR-148a, have been demonstrated to play important role in controlling the risk of CVD through regulation of cholesterol homeostasis and lipoprotein metabolism. lncRNAs are recently emerging as important regulators of lipid and lipoprotein metabolism. However, much additional work will be required to fully understand the impact of lncRNAs on CVD and lipid metabolism, due to the high abundance of lncRNAs and the poor-genetic conservation between species. This article reviews the role of miRNAs and lncRNAs in lipid and lipoprotein metabolism and their potential implications for the treatment of CVD.
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