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Background  In spite of clinical progress, cardiovascular disease (CVD) remains the predominant cause of mortality worldwide. Overexpression studies in animals have proven miR-424-5p to have anti-angiogenic properties. As type 1 diabetes mellitus (T1DM) without CVD displays endothelial dysfunction and reduced circulating endothelial progenitor cells (cEPCs), it offers a model of subclinical CVD. Therefore, we explored miR-424-5p, cytokines and vascular health in T1DM.    Methods  Twenty-nine well-controlled T1DM patients with no CVD and 20-matched controls were studied. Cytokines IL8, TNF-α, IL7, VEGF-C, cEPCs/CD45 dim CD34 + CD133 +  cells and ex-vivo proangiogenic cells (PACs)/fibronectin adhesion assay (FAA) were measured. MiR-424-5p in plasma and peripheral blood mononuclear cells (PBMC) along with mRNAs in PBMC was evaluated.    Results  We found an elevation of IL7 ( p  = 0.008), IL8 ( p  = 0.003), TNF-α ( p  = 0.041), VEGF-C ( p  = 0.013), upregulation of mRNA  CXCR1  ( p  = 0.009),  CXCR2  ( p  < 0.001) and reduction of cEPCs ( p  < 0.001), PACs ( p  < 0.001) and FAA ( p  = 0.017) in T1DM. MiR-424-5p was upregulated in T1DM in PBMC ( p  < 0.001). MiR-424-5p was negatively correlated with cEPCs ( p  = 0.006), PACs ( p  = 0.005) and FAA ( p  < 0.001) and positively with HbA 1c  ( p  < 0.001), IL7 ( p  = 0.008), IL8 ( p  = 0.017), VEGF-C ( p  = 0.007),  CXCR1  ( p  = 0.02) and  CXCR2  ( p  = 0.001). ROC curve analyses showed (1) miR-424-5p to be a biomarker for T1DM ( p  < 0.001) and (2) significant upregulation of miR-424-5p, defining subclinical CVD, occurred at HbA 1c  of 46.5 mmol/mol ( p  = 0.002).    Conclusion  We validated animal research on anti-angiogenic properties of miR-424-5p in T1DM. MiR-424-5p may be a biomarker for onset of subclinical CVD at HbA 1c  of 46.5 mmol/mol (pre-diabetes). Thus, miR-424-5p has potential use for CVD monitoring whilst anti-miR-424-5p-based therapies may be used to reduce CVD morbidity/mortality in T1DM.

stem cell research and therapy

Upregulated anti-angiogenic miR-424-5p in type 1 diabetes (model of subclinical cardiovascular disease) correlates with endothelial progenitor cells, CXCR1/2 and other parameters of vascular health