Serum microRNA array analysis identifies miR-140-3p, miR-33b-3p and miR-671-3p as potential osteoarthritis biomarkers involved in metabolic processes.

Background: MicroRNAs (miRNAs) in circulation have emerged as promising biomarkers. In this study, we aimed to identify a circulating miRNA signature for osteoarthritis (OA) patients and in combination with bioinformatics analysis to evaluate the utility of selected differentially expressed miRNAs in the serum as potential OA biomarkers. Methods: Serum samples were collected from 12 primary OA patients, and 12 healthy individuals were screened using the Agilent Human miRNA Microarray platform interrogating 2549 miRNAs. Receiver Operating Characteristic (ROC) curves were constructed to evaluate the diagnostic performance of the deregulated miRNAs. Expression levels of selected miRNAs were validated by quantitative real-time PCR (qRT-PCR) in all serum and in articular cartilage samples from OA patients (n = 12) and healthy individuals (n = 7). Bioinformatics analysis was used to investigate the involved pathways and target genes for the above miRNAs. Results: We identified 279 differentially expressed miRNAs in the serum of OA patients compared to controls. Two hundred and five miRNAs (73.5%) were upregulated and 74 (26.5%) downregulated. ROC analysis revealed that 77 miRNAs had area under the curve (AUC) > 0.8 and p < 0.05. Bioinformatics analysis in the 77 miRNAs revealed that their target genes were involved in multiple signaling pathways associated with OA, among which FoxO, mTOR, Wnt, pI3K/akt, TGF-β signaling pathways, ECM-receptor interaction, and fatty acid biosynthesis. qRT-PCR validation in seven selected out of the 77 miRNAs revealed 3 significantly downregulated miRNAs (hsa-miR-33b-3p, hsa-miR-671-3p, and hsa-miR-140-3p) in the serum of OA patients, which were in silico predicted to be enriched in pathways involved in metabolic processes. Target-gene analysis of hsa-miR-140-3p, hsa-miR-33b-3p, and hsa-miR-671-3p revealed that InsR and IGFR1 were common targets of all three miRNAs, highlighting their involvement in regulation of metabolic processes that contribute to OA pathology. Hsa-miR-140-3p and hsa-miR-671-3p expression levels were consistently downregulated in articular cartilage of OA patients compared to healthy individuals. Conclusions: A serum miRNA signature was established for the first time using high density resolution miR-arrays in OA patients. We identified a three-miRNA signature, hsa-miR-140-3p, hsa-miR-671-3p, and hsa-miR-33b-3p, in the serum of OA patients, predicted to regulate metabolic processes, which could serve as a potential biomarker for the evaluation of OA risk and progression.Peer reviewedFinal Published versio

Interleukin 6 (rs1800795) gene polymorphism is associated with cardiovascular diseases

Cardiovascular diseases (CVD) are group of complex and multifactorial pathologies, in which interleukin-6 (IL- 6) gene polymorphisms have been associated with several components of the CVD. Thus, in this study, we thoroughly reviewed and meta-analyzed evidence on the association between the IL-6 (rs1800795) gene polymorphism and CVD. We systematically searched in the PubMed, Web of Sciences, and Scopus databases. The analyses were performed using five study groups based on (1) a combined pool of the overall populations, (2) the country of birth, (3) the continent of birth, (4) the diagnosis and (5) both location (country or continent) and diagnosis. The analysis included the allelic, homozygote, heterozygote, dominant and recessive models. The meta-analysisshowed that -174G>C (rs1800795) is a risk factor for CVD (allelic: OR=1.06, CI 95%=1.02-1.10. Z p value C (rs1800795) polymorphism have an increase in the risk of coronary artery disease under the hereditary models assessed in the study. Using robust data, we found that IL-6 (rs1800795) -174G>C gene polymorphism is associated with CVD risk

Evidence that Statins Protect Renal Function During Endovascular Repair of AAAs

Objectives: Several studies have documented a slight but significant deterioration of renal function after endovascular repair of abdominal aortic aneurysm (AAA) (EVAR). The aim of this retrospective study was therefore to investigate whether medication with statins may favourably affect perioperative renal function. Material and Methods: From January 2000 to January 2008, out of a total cohort of 287 elective patients receiving endovascular repair of their AAA or aortoiliac aneurysm, 127 patients were included in the present study, as their medication was reliably retrievable. Patients were divided according to whether their medication included statins (>3 months). Second, they were subdivided according to their supra- (SR) or infrarenal (IR) endograft fixation. Serum creatinine (SCr) and creatinine (CrCl) clearance were determined preoperatively, postoperatively, at 6 and 12 months. Patients with known pre-existing renal disease, with incorrect placement of the stent graft resulting in severe renal artery stenosis, and with occlusion or renal parenchymal infarction were excluded from the study. Results: Patients receiving an infrarenal fixation of their graft had no change in the renal function, regardless whether they were on statins or not. In patients with SR fixation not receiving statins, a deterioration in renal function was observed in the early postoperative period ((SCr) preoperative vs. SCr postoperative: 1.02 +/- 0.2 vs. 1.11 +/- 0.28, p < 0.001 and (Cr.Cl) preoperative vs. Cr.Cl postoperative: 74.1 +/- 21.4 vs. 68.0 +/- 21.4, p<0.001), whereas patients on statins experienced no change in renal function (SCr preoperative vs. SCr postoperative: 0.99 +/- 0.24 vs. 1.02 +/- 0.20 n.s. and Cr.Cl preop vs. Cr.Clpostop.: 76.4 +/- 19.1 vs. 74.28 +/- 20.50, n.s.). During follow-up, a constant worsening of renal function at 6 and 12 months was observed, irrespective of the medication with statins. Conclusions: The present study suggests a slight immediate deterioration of the renal function using (SR) fixation, and this could be prevented by the use of statins. During follow-up, statins did not protect from further renal deterioration. Broader studies are needed to confirm a definitive relation between statin use and renal protection during the endovascular repair of AAA. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved