Oxidized LDL-regulated microRNAs for evaluating vascular endothelial function: molecular mechanisms and potential biomarker roles in atherosclerosis

Abstract

As a simple monolayer, vascular endothelial cells can respond to physicochemical stimuli. In addition to promoting the formation of foam cells, oxidized low-density lipoprotein (ox-LDL) contributes to the atherosclerotic process through different mechanisms, including endothelial cell dysfunction. As conserved noncoding RNAs, microRNAs (miRNAs) naturally lie in different genomic positions and post-transcriptionally regulate the expression of many genes. They participate in integrated networks formed under stress to maintain cellular homeostasis, vascular inflammation, and metabolism. These small RNAs constitute therapeutic targets in different diseases, including atherosclerosis, and their role as biomarkers is crucial given their detectability even years before the emergence of diseases. This review was performed to investigate the role of ox-LDL-regulated miRNAs in atherosclerosis, their molecular mechanisms, and their application as biomarkers of vascular endothelial cell dysfunction.

Keywords:

• Endothelial cells
• oxidized low-density lipoprotein
• microRNAs
• biomarkers
• atherosclerosis

Disclosure statement

No potential conflict of interest was reported by the author(s).

Figure 1. Ox-LDL-regulated microRNAs contribute to regulating the PI3K/Akt/mTOR and PI3K/Akt/eNOS signaling pathways, potentially influencing vascular endothelial cells. eNOS: endothelial nitric oxide synthase; miR: microRNA; mTOR: mammalian target of rapamycin; ox-LDL: oxidized low-density lipoprotein; PI3K/Akt: phosphatidylinositol 3-kinase/protein kinase B; Rheb: ras homolog enriched in brain; SMO: smoothened.

Figure 2. Ox-LDL-regulated microRNAs contribute to regulating TLR4 and MAPK pathway, which can affect atherosclerosis. miR: microRNA; MAPK: mitogen-activated protein kinase; ox-LDL: oxidized low-density lipoprotein; TLR4: toll-like receptor 4.

Table 1. Summary of studies on ox-LDL-upregulated microRNAs that affect vascular endothelial function and atherosclerosis.

Table 2. Summary of studies on ox-LDL-downregulated microRNAs that affect vascular endothelial function and atherosclerosis.