Dataset Information

Circulating "LncPPAR?" From Monocytes as a Novel Biomarker for Coronary Artery Diseases.

ABSTRACT: To investigate long noncoding RNA NONHSAT112178 (LncPPAR?) as a biomarker for coronary artery disease (CAD) in peripheral blood monocyte cells, RT-qPCR was performed to validate the microarray results, receiver operating characteristic curve was applied to study the potential of LncPPAR? as a biomarker. Diagnostic models from LncPPAR? alone or combination of risk factors were constructed by Fisher criteria. The expression of genes neighboring the LncPPAR? gene was examined with RT-qPCR in THP-1 cell line treated with LncPPAR? siRNA. Using a diagnostic model by Fisher criteria, the consideration of risk factors increased the optimal sensitivity from 70.00% to 82.00% and decreased the specificity from 94.00% to 78.00%. The consideration of risk factors also increased area under the receiver operating characteristic curve from 0.727 to 0.785 (P?=?0.001), from 0.712 to 0.768 (P?=?0.01), and from 0.769 to 0.835 (P?=?0.07), in the original, training, and test sets, respectively. Finally, we found that the expression of peroxisome proliferator-activated receptor ? (PPAR?), Adipose Differentiation-Related Protein (ADRP), and Angiopoietin-like 4 (ANGPTL4) were affected by LncPPAR? silencing.Our present study indicated that LncPPAR?, especially combined with risk factors, can be a good biomarker for CAD. LncPPAR? regulates the expression of neighboring protein-coding genes, PPAR? and its direct target genes ADRP and ANGPTL4.

SUBMITTER: Cai Y

PROVIDER: S-EPMC4753863 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Circulating "LncPPARδ" From Monocytes as a Novel Biomarker for Coronary Artery Diseases.

Cai Yue Y Yang Yujia Y Chen Xiongwen X He Duofeng D Zhang Xiaoqun X Wen Xiulan X Hu Jiayong J Fu Chunjiang C Qiu Dongfeng D Jose Pedro A PA Zeng Chunyu C Zhou Lin L

Medicine 20160201 6

To investigate long noncoding RNA NONHSAT112178 (LncPPARδ) as a biomarker for coronary artery disease (CAD) in peripheral blood monocyte cells, RT-qPCR was performed to validate the microarray results, receiver operating characteristic curve was applied to study the potential of LncPPARδ as a biomarker. Diagnostic models from LncPPARδ alone or combination of risk factors were constructed by Fisher criteria. The expression of genes neighboring the LncPPARδ gene was examined with RT-qPCR in THP-1 ...[more]

PMID: 26871769

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Project description:Exosomal miRNAs are currently being explored as a novel class of biomarkers in cardiovascular diseases. However, few reports have focused on the value of circulating exosomal miRNAs as biomarkers for stable coronary artery disease (SCAD). Here, we aimed to investigate whether miRNAs involved in cardiovascular diseases in circulating exosomes could serve as novel diagnostic biomarkers for SCAD. Firstly, the serum exosomes were isolated and purified by the ExoQuick reagent and identified by transmission electron microscopy, western blot, and nanoparticle tracking analysis. Then, the purified exosomes were quantified by measuring the exosome protein concentration and calculating the total protein amount. Next, eight miRNAs involved in cardiovascular diseases, miR-192-5p, miR-148b-3p, miR-125a-3p, miR-942-5p, miR-149-5p, miR-32-5p, miR-144-3p, and miR-142-5p, were quantified in circulating exosomes from the control group (n = 20) and the SCAD group (n = 20) by quantitative real-time polymerase chain reaction (qPCR). Finally, the gene targets of the differentially expressed miRNAs were predicted, and the functions and signaling pathways of these targets were analyzed using an online database. The isolated exosomes had a bilayer membrane with a diameter of about 100 nm and expressed exosomal markers including CD63, Tsg101, and Flotillin but negatively expressed Calnexin. Both the exosome protein concentration and total protein amount exhibited no significant differences between the two groups. The qPCR assay demonstrated that among the eight miRNAs, the expression levels of miR-942-5p, miR-149-5p, and miR-32-5p in the serum exosomes from the SCAD group were significantly higher than that from the control group. And the three miRNAs for SCAD diagnosis exhibited AUC values of 0.693, 0.702, and 0.691, respectively. GO categories and signaling pathways analysis showed that some of the predictive targets of these miRNAs were involved in the pathophysiology processes of SCAD. In conclusion, our findings suggest that serum exosomal miR-942-5p, miR-149-5p, and miR-32-5p may serve as potential diagnostic biomarkers for SCAD.

Project description:Background Circulating proteins are exposed to vascular endothelial layer and influence their functions. Among them, adipsin is a member of the trypsin family of peptidases and is mainly secreted from adipocytes, monocytes, and macrophages, catalyzing the rate-limiting step of the alternative complement pathway. However, its pathophysiological role in cardiovascular disease remains to be elucidated. Here, we examined whether serum adipsin levels have a prognostic impact in patients with coronary artery disease. Methods and Results In 370 consecutive patients undergoing diagnostic coronary angiography, we performed a cytokine array analysis for screening serum levels of 50 cytokines/chemokines and growth factors. Among them, classification and regression analysis identified adipsin as the best biomarker for prediction of their long-term prognosis (median 71 months; interquartile range, 55-81 months). Kaplan-Meier curve showed that higher adipsin levels (≥400 ng/mL) were significantly associated with all-cause death (hazard ratio [HR], 4.2; 95% CI, 1.7-10.6 [P<0.001]) and rehospitalization (HR, 2.4; 95% CI, 1.7-3.5 [P<0.001]). Interestingly, higher high-sensitivity C-reactive protein levels (≥1 mg/L) were significantly correlated with all-cause death (HR, 3.2; 95% CI, 1.7-5.9 [P<0.001]) and rehospitalization (HR, 1.5, 95% CI, 1.1-1.9 [P<0.01]). Importantly, the combination of adipsin (≥400 ng/mL) and high-sensitivity C-reactive protein (≥1 mg/L) was more significantly associated with all-cause death (HR, 21.0; 95% CI, 2.9-154.1 [P<0.001]). Finally, the receiver operating characteristic curve demonstrated that serum adipsin levels predict the death caused by acute myocardial infarction in patients with coronary artery disease (C-statistic, 0.847). Conclusions These results indicate that adipsin is a novel biomarker that predicts all-cause death and rehospitalization in patients with coronary artery disease, demonstrating the novel aspects of the alternative complementary system in the pathogenesis of coronary artery disease.

Dataset Information

Circulating "LncPPAR?" From Monocytes as a Novel Biomarker for Coronary Artery Diseases.

Publications

Circulating "LncPPARδ" From Monocytes as a Novel Biomarker for Coronary Artery Diseases.

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