miRNAs and High-Density Lipoprotein metabolism

Abstract

Altered lipoprotein metabolism plays a key role during atherogenesis. For over 50 years, epidemiological data have fueled the proposal that HDL-cholesterol (HDL-c) in circulation is inversely correlated to cardiovascular risk. However, the atheroprotective role of HDL is currently the focus of much debate and remains an active field of research. The emerging picture from research in the past decade suggests that HDL function, rather than HDL-c content is important in disease. Recent developments demonstrate that miRNAs play an important role in fine-tuning the expression of key genes involved in HDL biogenesis, lipidation, and clearance, as well as in determining the amounts of HDL-c in circulation. Thus, it has been proposed that miRNAs that affect HDL metabolism might be exploited therapeutically in patients. Whether HDL-based therapies, alone or in combination with LDL-based treatments (e.g. statins), provide superior outcomes in patients has been recently questioned by human genetics studies and clinical trials. The switch in focus from “HDL-cholesterol” to “HDL function” opens a new paradigm to understand the physiology and therapeutic potential of HDL, and to find novel modulators of cardiovascular risk. In this review we summarize the current knowledge on the regulation of HDL metabolism and function by miRNAs.

Lipid Metabolism Alteration by Endocrine Disruptors in Animal Models: An Overview

“…Moreover, a chronic BPA-exposure impacted the miRNome in adult zebrafish and established an epigenome more susceptible to cancer development. After a 3 weeks exposure to 100 nM BPA, in the liver, 6,188 mRNAs and 15 miRNAs were differently expressed ( q ≤ 0.1), uncovering signatures associated with NAFLD, oxidative phosphorylation, mitochondrial dysfunction and cell cycle, suggesting BPA potentiality to cause adverse health outcomes including cancer ( 66 ), and supporting previous studies evidencing the miRNA pivotal role in lipid synthesis, oxidation and related diseases ( 67 ). The expression of four miRNAs, miR-125b, miR-205, miR-142a, and miR-203a were significantly modulated by TCS in different experimental models both in vivo and in vitro ( 55 ), and resulted implicated in the downstream regulation of genes responsible for FA synthesis and metabolism.…”

Ageing influences the relationship of circulating miR-33a and miR-33b levels with insulin resistance and adiposity

“…35 According to this, the expression of miR-33 is closely related to the metabolism of HDLc. 36 In this study, we did not find differences in HDLc levels between individuals with and without IR, together with a significant increase in triglyceride and TC levels. Our previous works also show similar lipid profile and no differences in HDLc levels in our population with IR versus without IR.…”

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

“…Meanwhile, miRNAs have also emerged as the important regulators on HDL metabolism. Several studies demonstrated that miRNAs control the expression of a large number of genes associated with HDL metabolism, including ABCA1, ABCG1, and SR-BI [209,210]. These findings strongly suggested that miRNAs regulate HDL biogenesis, cholesterol efflux, and uptake in the liver, thereby controlling the whole RCT process [211,212].…”