MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases

Abstract

The regulation of the metabolism of cholesterol has been one of the most studied biological processes since its first isolation from gallstones in 1784. High levels of plasma low-density lipoprotein (LDL) cholesterol and reduced levels of plasma high-density lipoprotein (HDL) cholesterol are widely recognized as major risk factors of cardiovascular disease. An imbalance in the production of reactive oxygen species can oxidize LDL particles, increasing the levels of the highly proatherogenic oxidized LDL. Furthermore, under pathological scenarios, numerous molecules can function as pro-oxidants, such as iron or (high levels of) glucose. In addition to the classical mechanisms regulating lipid homeostasis, recent studies have demonstrated the important role of microRNAs (miRNAs) as regulators of lipoprotein metabolism, oxidative derivatives of lipoprotein, and redox balance. Here, we summarize recent findings in the field, highlighting the contributions of some miRNAs to lipid- and oxidative-associated pathologies. We also discuss how therapeutic intervention of miRNAs may be a promising strategy to decrease LDL, increase HDL, and ameliorate lipid- and oxidative-related disorders, including atherosclerosis, nonalcoholic fatty liver disease, and metabolic syndrome.

Keywords: Atherosclerosis; Free radicals; Lipid metabolism; MiRNAs.

Figure 1. Schematic overview of miRNAs involved in lipid metabolism and ROS

Different miRNAs are grouped in boxes and /or representative organs in which they target lipid metabolism regulators. Biological processes in which they are involved are also shown. ↑ indicates activation, ⊤ indicates inhibition.

Figure 2. Overview of the potential roles of miRNAs in atherosclerosis

A schematic picture of the pathological scenario in the atherosclerotic plaque. Boxes represent different biological processes implicated in atherosclerotic disease, such as inflammation, monocyte extravasation, apoptosis, oxidative stress or extracellular miRNAs. MiRNAs can modulate either positively or negatively several of these processes. ↑ indicates activation, ⊤ indicates inhibition.