The Role of miR-342 in Vascular Health. Study in Subclinical Cardiovascular Disease in Mononuclear Cells, Plasma, Inflammatory Cytokines and PANX2.

Sabina L Ray,Jevi Septyani Latief,Alice Tamara,Megan Li Yuen Yeoh,Jolanta U Weaver,Sherin Bakhashab,David J Coulson

doi:10.3390/ijms21197217

Abstract

Cardiovascular disease (CVD) correlates with inflammation and a reduction in circulating endothelial progenitor cells (cEPCs). Recently, CVD was shown to be the main cause of mortality in individuals with type 1 diabetes (T1DM). In animals, miR-342 was shown to exert an anti-inflammatory effect in CVD. Hypothesis: miR-342-3p/-5p are downregulated in subclinical CVD (T1DM), whereas inflammatory cytokines are upregulated. We studied miR -342 -3p/5p in plasma/peripheral blood mononuclear cells (PBMCs) in 29 T1DM and 20 controls (HC). Vascular health was measured by fibronectin adhesion assay (FAA), cEPCs (CD45dimCD34+133+ cells) and by assessing inflammation and tissue inhibition of metalloproteases (TIMP-1). In T1DM IL-7, IL-8, TNFα and VEGF-C were increased in plasma. MiR-342-3p/-5p were downregulated in PBMCs in T1DM, but not in plasma. PANX2, chemokine receptors CXCR1/2 mRNAs, were increased in PBMCs in T1DM. MiR-342-3p was negatively correlated with TIMP-1, IL-6, IL-8, TNF-α, HbA1c and CXCR2, whilst miR-342-5p was negatively correlated with TIMP-1, IL-6, IL-8 and HbA1c. There was a positive correlation among miR-342-3p, FAA and cEPCs, and between miR-342-5p and cEPCs. ROC curve analyses showed significant downregulation of miR-342-3p/-5p at HbA1c > 46.45 mmol/mol, indicating their potential as biomarkers for subclinical CVD. Our findings validated animal studies and confirmed the proangiogenic properties of miR-342-3p/-5p. MiR-342-3p/-5p-based intervention or monitoring may prove to be beneficial in managing CVD.

Highlights

Inflammatory processes have been shown to be key for the development and complications of cardiovascular disease (CVD) [1]
Patients with type 1 diabetes mellitus (T1DM) were characterized by a significant endothelial dysfunction, inflammatory state, reduced circulating endothelial progenitor cells, pro-angiogenic cells (PACs) and colony forming units (Hills)
To our knowledge, we are the first to demonstrate a negative correlation between miR-342-3p/-5p and glycemic control, TIMP-1, TNF-α and pro-inflammatory cytokine receptor CXCR2, as well as positive correlations between miR-342-3p/-5p and vascular health; fibronectin adhesion assay (FAA) and CD45dimCD34+CD133+ cells, otherwise known as early endothelial progenitor cells

Summary

Introduction

Inflammatory processes have been shown to be key for the development and complications of cardiovascular disease (CVD) [1]. We have previously published evidence to suggest that T1DM has features of early CVD without documented or apparent CVD events [3,4,5]. Patients with T1DM were characterized by a significant endothelial dysfunction, inflammatory state, reduced circulating endothelial progenitor cells (cEPCs), pro-angiogenic cells (PACs) and colony forming units (Hills). All of those vascular health indicators have been noted to characterize CVD in other patient groups [6,7]. Evidence suggests CVD is strongly correlated and predicted by the markers of vascular health listed above, other biomarkers are becoming apparent, including microRNAs (miRNA) [8]

Methods

Discussion

Conclusion