Conclusions The miR-33 family exhibits differences in distribution and regulation and particularly in the progression of atherosclerosis; miR-33b would be more potent than miR-33a.
The miR-33 microRNAs (miRNAs) are crucial regulators of cholesterol/lipids, and may represent therapeutic targets for the treatment of atherosclerosis.A recent report by Price et al. showed that miR-33 knockout (KO) mice exhibit obesity, insulin resistance, and increased food intake, suggesting that metabolic regulation by miR-33 is more complex than was previously known.
We showed that miR-200c induces endothelial dysfunction, ROS production and a positive mechanism among miR-200c and miR-33a/b, two miRNAs involved in atherosclerosis progression.
Previous studies suggested that miR-33 (microRNA-33) inhibition and genetic ablation of miR-33 increased serum high-density lipoprotein cholesterol and attenuated atherosclerosis.
A highly conserved microRNA (miR), miR-33, is considered as a potential therapeutic target for atherosclerosis because it regulates lipid metabolism and inflammation.
By controlling the expression levels of their targets, several miRNAs have been shown to modulate the function of endothelial cells (miR-221/222 and -126), vascular smooth muscle cells (miR-143/145) and macrophages (miR-33, -758, and -26), thereby regulating the development and progression of atherosclerosis.
Therefore, the pro-atherogenic effects observed in miR-33-deficient mice are likely counterbalanced by protective effects in macrophages, which may be the primary mechanism through which anti-miR-33 therapies reduce atherosclerosis.
MicroRNA-33 (miR-33), a novel non-coding RNA that coexpresses with sterol regulatory element-binding proteins (SREBPs), affects macrophage actions to prevent atherosclerosis.
Expression of miR-33a/b was markedly increased in human carotid atherosclerotic plaques compared with normal arteries, and there was a concomitant decrease in mitochondrial regulatory genes PGC-1α, SLC25A25, NRF1, and TFAM, suggesting these genes are associated with advanced atherosclerosis in humans.
As we are now living in a period of "satiation", miR-33a/b no longer seem to be useful and could be potential therapeutic targets for lipid disorders and/or atherosclerosis.
In particular, miR122 and miR-33 have a significant impact on lipid homeostasis and are potential therapeutic targets for treating lipid disorders and/or atherosclerosis.
Recent reports have indicated that miR-33, which is located within the intron of sterol regulatory element-binding protein (SREBP) 2, controls cholesterol homoeostasis and may be a potential therapeutic target for the treatment of atherosclerosis.
Understanding the etiology and pathophysiology of microRNA-33 in atherosclerosis may provide basic knowledge for the development of novel therapeutic targets for ameliorating atherosclerosis and cardiovascular disease.
This review surveys the impact of microRNA-mediated regulation in biological processes governing the cholesterol/lipoprotein metabolism, fatty acid β-oxidation (eg by miR-122 and miR-33), and endothelial dysfunction related to atherosclerosis.
These studies establish that raising HDL levels by anti-miR33 oligonucleotide treatment promotes reverse cholesterol transport and atherosclerosis regression and suggest that it may be a promising strategy to treat atherosclerotic vascular disease.