There is an intensive effort to identify biomarkers to predict cardiovascular disease evolution. We aimed to determine the potential of microRNAs to predict the appearance of cardiovascular events (CVEs) in patients with peripheral artery disease (PAD) following femoral artery bypass surgery. Forty-seven PAD patients were enrolled and divided into two groups, without CVEs (n = 35) and with CVEs (n = 12), during 1 year follow-up. Intra-surgery atherosclerotic plaques from femoral arteries were collected and the levels of miR-142, miR-223, miR-155, and miR-92a of the primary transcripts of these microRNAs (pri-miRNAs), and gene expression of Drosha and Dicer were determined. Results showed that, in the plaques, miR-142, miR-223, and miR-155 expression levels were significantly increased in PAD patients with CVEs compared to those without CVEs. Positive correlations between these miRNAs and their pri-miRNAs levels and the Dicer/Drosha expression were observed. In the plasma of PAD patients with CVEs compared to those without CVEs, miR-223 and miR-142 were significantly increased. The multiple linear regression analyses revealed significant associations among several plasma lipids, oxidative and inflammatory parameters, and plasma miRNAs levels. Receiver operator characteristic (ROC) analysis disclosed that plasma miR-142 levels could be an independent predictor for CVEs in PAD patients. Functional bioinformatics analyses supported the role of these miRNAs in the regulation of biological processes associated with atherosclerosis. Taken together, these data suggest that plasma levels of miR-142, miR-223, miR-155, and miR-92a can significantly predict CVEs among PAD patients with good accuracy, and that plasma levels of miR-142 can be an independent biomarker to predict post-surgery CVEs development in PAD patients.
Peripheral artery disease (PAD) is an atherosclerotic disorder affecting arteries of the lower limbs, the major risk factors including dyslipidemia and diabetes mellitus (DM). We aimed to identify alterations of the proteins in high-density lipoproteins (HDL) associated with HDL dysfunction in PAD patients. HDL 2 and HDL 3 were isolated from plasma of PAD patients with/without DM (PAD-DM/PAD) and healthy subjects (N). Apolipoprotein AI (ApoAI), ApoAII, ApoCIII, clusterin (CLU), paraoxonase 1 (PON1), myeloperoxidase (MPO), and ceruloplasmin (CP) were measured in HDL 2 /HDL 3 and plasma. Oxidation and glycation of the analyzed proteins were assessed as malondialdehyde-protein adducts (MDA) and advanced glycation end-products (AGE), respectively. The anti-inflammatory effect of HDL 3 was estimated as its potential to reduce monocyte adhesion to tumor necrosis factor α-activated endothelial cells. We show that in PAD patients compared to N subjects: (i) HDL 2 presented increased levels of MDA-PON1, AGE-PON1, AGE-ApoAI, ApoAII, ApoCIII, and CP levels, and decreased PON1 levels; (ii) HDL 3 had increased levels of MDA-and AGE-CLU and -ApoAI, MDA-PON1, ApoCIII, CLU, MPO, CP, and reduced PON1 levels. All these alterations were exacerbated by DM. These changes were more pronounced in HDL 3 , which had reduced antiinflammatory potential in PAD and became pro-inflammatory in PAD-DM. In PAD patients' plasma, CLU levels and MPO specific activity increased, while PON1 specific activity decreased. In conclusion, HDL function
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