miR-155 in the Resolution of Atherosclerosis

Abstract

Atherosclerosis is a chronic progressive inflammatory disease where advanced lesions can eventually completely obstruct blood flow resulting in clinical events, such as a myocardial infarction or stroke. Monocytes and macrophages are the dominant biologically active immune cells involved in atherosclerosis disease and play a pivotal role during initiation, progression, and regression of disease. Altering macrophage inflammation is critical to induce regression of atherosclerosis and microRNAs (miRs) have emerged as key regulators of the macrophage phenotype. MiRs are small noncoding RNAs that regulate gene expression. They are dysregulated during atherosclerosis development and are key regulators of macrophage function and polarization. MiRs are short nucleotide transcripts that are very stable in circulation and thus have potential as therapeutics and/or biomarkers in the context of atherosclerosis. Of relevance to this review is that inhibition of macrophage-specific miR-155 may be a viable therapeutic strategy to decrease inflammation associated with atherosclerosis. However, further studies on these miRs and advancements in miR therapeutic delivery are required for these therapeutics to advance to the clinical setting. Conjugated linoleic acid (CLA), a pro-resolving lipid mediator, is an agonist of the peroxisome proliferator-activated receptor (PPAR)-γ. The biological activities of CLA have been documented to have anti-atherogenic effects in experimental models of atherosclerosis, inducing regression and impacting on monocyte and macrophage cells. Our work and that of others on PPAR-γ agonists and polyunsaturated fatty acids have shown that these mediators regulate candidate miRNAs and promote pro-resolving atherosclerotic plaque microenvironments.

MiRNAs as biomarkers of phenotype in neutral lipid storage disease with myopathy

“…Finally, our results also showed an increase of miR‐155 in NLSDM patients in comparison to the control group. MiR‐155 has important functions in inflammation and, recently, was described to contribute to liver pathology and arteriosclerosis …”

MicroRNAs: New Biomarkers for the progression of Coronary Artery Diseases

“…Li et al [33] suggested that the increased level of miR-155 could relieve inflammation and foam cell formation via the signaling pathway of miR-155-CARHSP1-TNF-α, but it was also claimed that the anti-inflammatory function of HDL is conferred through miRNA-33. Besides, miR-33 inhibition in macrophages has been verified to be able to enhance cholesterol efflux and reduce As lesions in mice [32] . Additionally, miR-21, a pro-survival gene for VSMCs, is another important miRNA in As, which has been demonstrated to be capable of impacting neointimal formation [28] .…”

“…Recently, multiple studies have reported that miRNAs are dysregulated during the development of As ( Table 2), for example, several miRNAs such as miR-155, miR-33 are upregulated in As [30,32] . Considering the function of miRNAs in macrophage polarization, they may be able to serve as important regulators and predictors for As.…”

“…Among the multiple dysregulated miRNAs in As, miR-155 and miR-33 have also been thought as the potential targets to decelerate the development of As. miR-155 is upregulated in response to pro-inflammatory stimulants, and its repression may be a viable strategy to reduce the inflammatory response [32] . Li et al [33] suggested that the increased level of miR-155 could relieve inflammation and foam cell formation via the signaling pathway of miR-155-CARHSP1-TNF-α, but it was also claimed that the anti-inflammatory function of HDL is conferred through miRNA-33.…”

“…Pentraxin 3 (PTX-3) [35] LOX-1 * [31] RANTES * [31] miR-33 [32,38] miR-155 [32] HF Natriuretic peptide [39] miR-1 [40] miR-21 [41] miR-132 [42] ISR CD45þ platelet count [43] C-reactive protein [44] miR-143 [45] miR-93-5p [46] CK-MB * : Creatine kinase-MB; LOX-1 * : Lectin-like oxidized LDL receptor-1; RANTES * : Regulated on activation, normal T cellexpressed and secreted Table 2. miRNAs associated with As, AMI, HF and ISR…”