[Show abstract][Hide abstract] ABSTRACT: Background
Recent studies indicated that microRNAs (miRNAs, miRs) were important for many biological and pathological processes, and they might be potential biomarkers for cardiovascular diseases. The present study aims to determine the release patterns of miRNAs in cardiac surgery and to analyze the ability of miRs to provide early prediction of perioperative myocardial infarction (PMI) in patients undergoing coronary artery bypass graft (CABG) surgery.
Thirty on-pump CABG patients were recruited in this study; and miR-499, miR-133a and miR-133b, cardiac troponin I (cTnI) were selected for measurement. Serial plasma samples were collected at seven perioperative time points (preoperatively, and 1, 3, 6, 12, 24, and 48 hours after declamping) and were tested for cTnI and miRs levels. Importantly, miR levels peaked as early as 1–3 hours, whereas cTnI levels peaked at 6 hours after declamping. Peak plasma concentrations of miRs correlated significantly with cTnI (miR-499, r = 0.583, P = 0.001; miR-133a, r = 0.514, P = 0.006; miR-133b, r = 0.437, P = 0.05), indicating the degree of myocardial damage. In addition, 30 off-pump CABG patients were recruited; miR-499 and miR-133a levels were tested, which were significantly lower in off-pump group than in on-pump group. A prospective cohort of CABG patients (n = 120) was recruited to study the predictive power of miRs for PMI. The diagnosis of PMI strictly adhered to the principles of universal definition of myocardial infarction. The data analysis revealed that miR-499 had higher sensitivity and specificity than cTnI, and indicated that miR-499 could be an independent risk factor for PMI.
Our results demonstrate that circulating miR-499 is a novel, early biomarker for identifying perioperative myocardial infarction in cardiac surgery.
PLoS ONE 08/2014; 9(8):e104618. DOI:10.1371/journal.pone.0104618 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe acute kidney injury (AKI) after cardiac surgery is associated with poor clinical outcomes. This study evaluated the potential use of miR-21 as a risk marker for postoperative AKI progression and other poor outcomes.
The study included 120 adult patients undergoing cardiac surgery: 40 non-AKI controls, 39 patients with progressive AKI, and 41 with non-progressive AKI. Urine and plasma levels of miR-21 were assessed by quantitative real-time PCR (RT-qPCR). Associations between miR-21 levels and AKI progression were determined by estimating areas under receiver operating characteristic curves (AUC). We demonstrated that up-regulated urine and plasma levels of miR-21 in patients with AKI were both associated with AKI progression. The AUCs for urine and plasma levels of miR-21 associated with established AKI were 0.68 (95%CI: 0.59-0.78) and 0.80 (95%CI: 0.73-0.88), respectively. Multiple logistic regression analysis, adjusting for clinical variables, indicated that the prognostic predictive power of urine and plasma miR-21 levels for AKI progression were represented by AUCs of 0.81 (95%CI: 0.72-0.91) and 0.83 (95%CI: 0.74-0.92), respectively. Urinary and plasma miR-21 levels also predicted the need for postoperative renal replacement therapy (RRT), development of Acute Kidney Injury Network (AKIN) stage 3 AKI, 30-day in-hospital mortality and prolonged stay in hospital or ICU. Urine miR-21 was a better outcome predictor than plasma miR-21, being associated with higher (1.4- to 2.6-fold) unadjusted odds ratio for progression of AKI and other poor outcomes.
Urinary and plasma miR-21 are associated with severe AKI and other poor postoperative outcomes of cardiac surgery, indicating their potential use as prognostic markers.
PLoS ONE 05/2013; 8(5):e63390. DOI:10.1371/journal.pone.0063390 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Recent studies demonstrated that the mammalian heart possesses some capacity to proliferate. We observed cardiomyocyte proliferation within 4 weeks of age (P4W) in rats. We found 95 microRNAs that are differentially expressed in P4W cardiomyocytes. MicroRNA-29a was among the most highly up-regulated microRNAs in P4W cardiomyocytes. Overexpression of microRNA-29a suppressed the proliferation of H9c2 cell line. MicroRNA-29a inhibition induced cardiomyocytes to proliferate, accelerated the G1/S and G2/M transition, and up-regulated the cell cycle gene expression. Cyclin D2 (CCND2) was identified as a direct target of microRNA-29a. These findings indicate that microRNA-29a is involved in cardiomyocyte proliferation during postnatal development.
[Show abstract][Hide abstract] ABSTRACT: Cyclin D1 (CCND1) plays a critical role in the G1 to S-phase cell cycle transition. Data on the association between the CCND1 A870G polymorphism and oral cancer are conflicting. To assess the relationship between the CCND1 A870G genotype and the risk of developing oral cancer, we performed a meta-analysis. We searched PubMed to December 1, 2011, for studies on this topic that had been published in the English. For each study, we calculated odds ratios (ORs) and 95 % confidence intervals (CIs), assuming the frequency of allele comparison, homozygote comparison, recessive and dominant genetic models. We then calculated pooled ORs and 95 % CIs. Seven studies were included in the meta-analysis. The CCND1 G allele was not associated with oral cancer in the frequency of allele comparison (G vs. A: OR = 0.882; 95 % CI = 0.684-1.137; p = 0.001 for heterogeneity). In the subgroup analysis, the CCND1 G allele was associated with a borderline significantly decreased risk of developing oral cancer in Asians in the frequency of allele comparison (G vs. A: OR = 0.800; 95 % CI = 0.636-1.006; p = 0.089 for heterogeneity), and the association between the GG genotype and oral cancer was significant in Asians with respect to both the homozygote comparison (GG vs. AA: OR = 0.644; 95 % CI = 0.491-0.843; p = 0.186 for heterogeneity) and the dominant genetic model (GG + AG vs. AA: OR = 0.713; 95 % CI = 0.584-0.870; p = 0.293 for heterogeneity). Our analysis provides evidence that genotypes for the CCND1 A870G polymorphism may be associated with an increased risk of developing oral cancer in the Asian population.
[Show abstract][Hide abstract] ABSTRACT: Cardiac fibrosis after myocardial infarction (MI) has been identified as a key factor in the development of heart failure. Although dysregulation of microRNA (miRNA) is involved in various pathophysiological processes in the heart, the role of miRNA in fibrosis regulation after MI is not clear. Previously we observed the correlation between fibrosis and the miR-24 expression in hypertrophic hearts, herein we assessed how miR-24 regulates fibrosis after MI. Using qRT-PCR, we showed that miR-24 was down-regulated in the MI heart; the change in miR-24 expression was closely related to extracellular matrix (ECM) remodelling. In vivo, miR-24 could improve heart function and attenuate fibrosis in the infarct border zone of the heart two weeks after MI through intramyocardial injection of Lentiviruses. Moreover, in vitro experiments suggested that up-regulation of miR-24 by synthetic miR-24 precursors could reduce fibrosis and also decrease the differentiation and migration of cardiac fibroblasts (CFs). TGF-β (a pathological mediator of fibrotic disease) increased miR-24 expression, overexpression of miR-24 reduced TGF-β secretion and Smad2/3 phosphorylation in CFs. By performing microarray analyses and bioinformatics analyses, we found furin to be a potential target for miR-24 in fibrosis (furin is a protease which controls latent TGF-β activation processing). Finally, we demonstrated that protein and mRNA levels of furin were regulated by miR-24 in CFs. These findings suggest that miR-24 has a critical role in CF function and cardiac fibrosis after MI through a furin-TGF-β pathway. Thus, miR-24 may be used as a target for treatment of MI and other fibrotic heart diseases.
Journal of Cellular and Molecular Medicine 01/2012; 16(9):2150-60. DOI:10.1111/j.1582-4934.2012.01523.x · 4.01 Impact Factor