microRNA expression signatures and parallels between monocyte subsets and atherosclerotic plaque in humans

Abstract

Small non-coding microRNAs (miRNAs) have emerged to play critical roles in cardiovascular biology. Monocytes critically drive atherosclerotic lesion formation, and can be subdivided into a classical and non-classical subset. Here we scrutinised the miRNA signature of human classical and non-classical monocytes, and compared miRNA expression profiles of atherosclerotic plaques from human carotid arteries and healthy arteries. We identified miRNAs to be differentially regulated with a two-fold or higher difference between classical and non-classical monocyte subsets. Moreover, comparing miRNA expression in atherosclerotic plaques compared to healthy arteries, we observed several miRNAs to be aberrantly expressed, with the majority of miRNAs displaying a two-fold or higher increase in plaques and only few miRNAs being decreased. To elucidate similarities in miRNA signatures between monocyte subsets and atherosclerotic plaque, expression of miRNAs highly abundant in monocytes and plaque tissues were compared. Several miRNAs were found in atherosclerotic plaques but not in healthy vessels or either monocyte subset. However, we could identify miRNAs co-expressed in plaque tissue and classical monocytes (miR-99b, miR-152), or non-classical monocytes (miR-422a), or in both monocytes subsets. We thus unravelled candidate miRNAs, which may facilitate our understanding of monocyte recruitment and fate during atherosclerosis, and may serve as therapeutic targets for treating inflammatory vascular diseases.

Dissecting the Roles of MicroRNAs in Coronary Heart Disease via Integrative Genomic Analyses

“…A volcano plot (Supplementary Figure I) revealed that these 15 miRNAs all had increased expression in CHD cases compared to controls (fold change ranged from 1.20 to 1.55 in average miRNA expression levels). Among the 15 “signature” miRNAs, miR-423-5p was previously identified as a circulating biomarker for heart failure in plasma 13 ; miR-422a was reported to be expressed in both monocytes and atherosclerotic plaque 22 . Analysis of miRNA data from three previously published studies revealed associations with cardiovascular disease for miR-191 13 , miR-589 13 , miR-423-5p 13 , 23 , miR-339-3p 23 , miR-422a 23 , 24 , miR-425 23 , miR-500 23 and miR-550 24 at p <0.05 in plasma 13 , 23 or platelets 24 .…”

“…Although the importance of miRNAs in cardiovascular development and disease is becoming increasingly recognized, the relations of miRNAs to CHD have been analyzed only in a few studies 12–15 , 22 . In this study, genome-wide genotyping and miRNA and mRNA expression profiling analysis were performed on 186 CHD case-control pairs.…”

“…First, our study identified 15 differentially expressed miRNAs in whole blood, all of which were upregulated in CHD cases. In a previous study, Bidzhekov et al identified 23 differentially expressed miRNAs in atherosclerotic plaques compared to healthy arteries, twenty of which displayed upregulation patterns in atherosclerotic plaques 22 . Therefore, the observed miRNA upregulation patterns in CHD were consistent between our study and that of Bidzhekov, suggesting that miRNAs may play an important role in CHD.…”

Pathway Analysis of MicroRNA Expression Profile during Murine Osteoclastogenesis

“…Previously, miR-99b was shown to be up-regulated in dendritic cells and monocytes during inflammation [23], [24]. In other cell types, miR-99b was shown to directly target components of the TNFα (tumor necrosis factor α) signaling pathway: Tnfα , Tnfrsf4 (Tumor Necrosis Factor Receptor Superfamily, Member 4), and Traf2 (TNF receptor-associated factor 2) [23], [25]–[27].…”

Therapeutic Potential of Modulating microRNAs in Atherosclerotic Vascular Disease

“…Nonetheless whether they should be considered a diagnostic or prognostic marker, a consequence or a cause is still a matter of debate [139]. MiRNA expression profiles comparing atherosclerotic plaques versus healthy arteries [44, 140] or plaques from symptomatic and asymptomatic subjects have also been performed [141]. Even though these studies provide useful information about the homeostasis of human atherosclerotic plaques, they usually fail to decipher the specific source (cellular and/or area of the plaque) and the molecular mechanisms underlying the role of these miRNAs.…”