Effects of ambient ozone exposure on circulating extracellular vehicle microRNA levels in coronary artery disease patients.
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ABSTRACT:
SUBMITTER: Chen H
PROVIDER: S-EPMC7306136 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundWe investigated the role of ANGPTL3 and ANGPTL4 in atherosclerosis development and determined whether plasma concentrations of ANGPTL3 and ANGPTL4 are related to the degree of coronary stenosis.MethodsA total of 305 consecutive patients with angina who underwent diagnostic coronary angiography were enrolled in the study between August 2017 and August 2018. The levels of ANGPTL3 and ANGPTL4 were measured by using competitive ELISA kits.ResultsAccording to the degree of coronary artery stenosis, patients were classified into four types: coronary artery stenosis of < 10%, 10-50%, 50-75, and > 75%. The plasma ANGPTL3 level was higher (51.71 ± 52.67 vs. 24.65 ± 10.32 ng/mL, P < 0.001) and that of ANGPTL4 was lower (454.66 ± 269.05 vs. 875.49 ± 961.15 ng/mL, P < 0.001) in the coronary artery stenosis ≥ 10% group than in the < 10% group. ANGPTL3 and ANGPTL4 levels were significantly associated with the severity of coronary vascular stenosis. ROC curve analyses indicated that ANGPTL3 concentrations above 30.5 ng/mL can predict atherosclerosis with a sensitivity of 71.2% and specificity of 75.3%, and that ANGPTL4 levels below 497.5 ng/mL can predict atherosclerosis with a sensitivity of 63.9% and specificity of 74.5%. ANGPTL3 and ANGPTL4 were determined to be independent risk factors for coronary atherosclerosis with odds ratios (ORs) of 0.189 (95% CI 0.097-0.368, P < 0.001) and 3.625 (95% CI 1.873-7.016, P < 0.001), respectively.ConclusionsIncreased ANGPTL3 or decreased ANGPTL4 shows an association with coronary atherosclerosis and, may become a predictor of coronary atherosclerosis in the future.
| S-EPMC8571829 | biostudies-literature
Project description:Genetic studies might provide new insights into the biological mechanisms underlying lipid metabolism and risk of CAD. We therefore conducted a genome-wide association study to identify novel genetic determinants of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides.We combined genome-wide association data from 8 studies, comprising up to 17 723 participants with information on circulating lipid concentrations. We did independent replication studies in up to 37 774 participants from 8 populations and also in a population of Indian Asian descent. We also assessed the association between single-nucleotide polymorphisms (SNPs) at lipid loci and risk of CAD in up to 9 633 cases and 38 684 controls. We identified 4 novel genetic loci that showed reproducible associations with lipids (probability values, 1.6×10(-8) to 3.1×10(-10)). These include a potentially functional SNP in the SLC39A8 gene for HDL-C, an SNP near the MYLIP/GMPR and PPP1R3B genes for LDL-C, and at the AFF1 gene for triglycerides. SNPs showing strong statistical association with 1 or more lipid traits at the CELSR2, APOB, APOE-C1-C4-C2 cluster, LPL, ZNF259-APOA5-A4-C3-A1 cluster and TRIB1 loci were also associated with CAD risk (probability values, 1.1×10(-3) to 1.2×10(-9)).We have identified 4 novel loci associated with circulating lipids. We also show that in addition to those that are largely associated with LDL-C, genetic loci mainly associated with circulating triglycerides and HDL-C are also associated with risk of CAD. These findings potentially provide new insights into the biological mechanisms underlying lipid metabolism and CAD risk.
| S-EPMC3891568 | biostudies-literature
Project description:Background Recent studies have revealed sexually dimorphic associations between the carbamoyl-phosphate synthase 1 locus, intermediates of the metabolic pathway leading from choline to urea, and risk of coronary artery disease ( CAD ) in women. Based on evidence from the literature, the atheroprotective association with carbamoyl-phosphate synthase 1 could be mediated by the strong genetic effect of this locus on increased circulating glycine levels. Methods and Results We sought to identify additional genetic determinants of circulating glycine levels by carrying out a meta-analysis of genome-wide association study data in up to 30 118 subjects of European ancestry. Mendelian randomization and other analytical approaches were used to determine whether glycine-associated variants were associated with CAD and traditional risk factors. Twelve loci were significantly associated with circulating glycine levels, 7 of which were not previously known to be involved in glycine metabolism ( ACADM , PHGDH , COX 18- ADAMTS 3, PSPH , TRIB 1, PTPRD , and ABO ). Glycine-raising alleles at several loci individually exhibited directionally consistent associations with decreased risk of CAD . However, these effects could not be attributed directly to glycine because of associations with other CAD -related traits. By comparison, genetic models that only included the 2 variants directly involved in glycine degradation and for which there were no other pleiotropic associations were not associated with risk of CAD or blood pressure, lipid levels, and obesity-related traits. Conclusions These results provide additional insight into the genetic architecture of glycine metabolism, but do not yield conclusive evidence for a causal relationship between circulating levels of this amino acid and risk of CAD in humans.
| S-EPMC6585317 | biostudies-literature
Project description:Background: Collateral artery growth, also termed arteriogenesis, occurs upon narrowing or occlusion of a major artery. To date, attempts to stimulate arteriogenesis in patients for therapeutic purposes have not been successful. Experimental models showed that circulating cells orchestrate arteriogenesis. In humans, a large heterogeneity exists in the arteriogenic response. We hypothesized that good arteriogenic responders (GARs) and bad arteriogenic responders (BARs) differ in gene expression profiles of circulating cells, thereby disclosing potential new therapeutic strategies for the stimulation of arteriogenesis. Methods: A total of 45 patients scheduled for percutaneous coronary intervention (PCI) for single-vessel coronary artery disease underwent intracoronary measurements of collateral flow index (CFI) to distinguish between GARs (CFI>0.21) and BARs (CFI≤0.21). Monocytes and CD34+ stem cells were collected from peripheral blood. A fraction of monocytes was further processed to obtain stimulated monocytes and macrophages. Whole genome transcriptome analysis was performed on all four cell types. Results: LPS-stimulated monocytes showed 244 genes differentially expressed (false discovery rate < 0.05) between GARs and BARs. Macrophage gene expression correlated with stimulated monocytes, while resting monocytes and stem cells revealed no differential gene expression. Stimulated monocytes from GARs showed a strongly attenuated response in several interferon- and apoptosis-related genes, which was corroborated at the protein level. Conclusions Circulating cells from GARs and BARs distinctively differ in their gene expression profiles upon stimulation. The reduced expression of interferon and apoptosis genes in GARs may lead to novel therapeutic approaches for the stimulation of collateral artery growth. Keywords: disease state analysis, stress response analysis, natural defense mechanism analysis
2008-04-17 | GSE7547 | GEO
Project description:BackgroundGalectin-3 plays a crucial role in the regulation of inflammation. The aim of this study was to elucidate the association between LGALS3 genotypes, galectin-3 levels, and inflammatory marker levels in patients with coronary artery disease (CAD).ResultsA total of 474 patients with CAD were enrolled. Significant correlations were discerned between galectin-3 levels and leukocyte counts, C-reactive protein, soluble intercellular adhesion molecule-1, and matrix metalloproteinase 9 levels (all p < .05). The LGALS3 rs2274273, rs4644, rs4652 genotypes, and haplotypes CAC, CCC, and ACT exhibited a significant association with galectin-3 levels (for genotypes, p = 1.05 × 10-25 , 3.54 × 10-25 , and 2.74 × 10-7 , respectively). Multivariate analysis showed LGALS3 rs2274273 and rs4644 genotypes contributing to 20.8% variation of galectin-3 levels. However, there was no association between LGALS3 genotypes and other inflammatory marker levels.ConclusionsOur data showed strong genetic determinants of galectin-3 levels in patients with CAD. The galectin-3 levels, but not LGALS3 genotypes, were associated with multiple inflammatory marker levels. Further study may be necessary to elucidate the molecular mechanism of galectin-3 in the pathogenesis of chronic inflammatory disorders.
| S-EPMC7507567 | biostudies-literature
Project description:Background and objectiveMicroRNAs (miRNAs) have been shown to be associated with various physiological and pathological conditions, including inflammation and cardiovascular disease, but little is known about their relationship with the presence of coronary artery disease (CAD) and disease severity.MethodsA total of 195 consecutive subjects who underwent coronary angiography for chest pain evaluation were enrolled in this study. In CAD patients severity of coronary lesions was assessed by the number of diseased vessels and the Synergy between PCI with Taxus and Cardiac surgery score (SYNTAX score). Plasma levels of miRNA-145 were quantified by real-time quantitative polymerase chain reaction test, and logarithmic transformation of miRNA-145 levels (Ln_miRNA-145) was used for analyses due to its skewed distribution.ResultsOf the 195 total subjects 167 patients were diagnosed as having CAD. Ln_miRNA-145 was significantly lower in CAD patients compared with the non-CAD group (-6.11 ± 0.92 vs. -5.06 ± 1.25; p < 0.001). In multivariable linear regression analyses CAD was significantly associated with lower Ln_miRNA-145 (Estimate, -0.50; standard error (SE), 0.11; p < 0.0001). Furthermore, among CAD patients, three-vessel disease, higher SYNTAX scores and STEMI were significantly associated with lower Ln_miRNA-145 ([Estimate, -0.40; SE, 0.07; p < 0.0001]; [Estimate, -0.02, SE, 0.10; p = 0.005] and [Estimate, -0.35, SE, 0.10; p < 0.001] respectively).ConclusionsLower plasma levels of miRNA-145 were significantly associated with the presence as well as severity of CAD. As a potential biomarker for CAD, plasma miRNA-145 may be useful in predicting CAD and its severity in patients presenting with chest pain.
| S-EPMC4418743 | biostudies-literature
Project description:Long-term ambient ozone (O3) exposure is a risk factor for human health. We estimate the source-specific disease burden associated with long-term O3 exposure in India at high spatial resolution using updated risk functions from the American Cancer Society Cancer Prevention Study II. We estimate 374,000 (95UI: 140,000-554,000) annual premature mortalities using the updated risk function in India in 2015, 200% larger than estimates using the earlier American Cancer Society Cancer Prevention Study II risk function. We find that land transport emissions dominate the source contribution to this disease burden (35%), followed by emissions from power generation (23%). With no change in emissions by 2050, we estimate 1,126,000 (95UI: 421,000-1,667,000) annual premature mortalities, an increase of 200% relative to 2015 due to population aging and growth increasing the number of people susceptible to air pollution. We find that the International Energy Agency New Policy Scenario provides small changes (+1%) to this increasing disease burden from the demographic transition. Under the International Energy Agency Clean Air Scenario we estimate 791,000 (95UI: 202,000-1,336,000) annual premature mortalities in 2050, avoiding 335,000 annual premature mortalities (45% of the increase) compared to the scenario of no emission change. Our study highlights that critical public health benefits are possible with stringent emission reductions, despite population growth and aging increasing the attributable disease burden from O3 exposure even under such strong emission reductions. The disease burden attributable to ambient fine particulate matter exposure dominates that from ambient O3 exposure in the present day, while in the future, they may be similar in magnitude.
| S-EPMC7007144 | biostudies-literature
Project description:In the present study, we performed transcriptome expression analyses in three independent peripheral blood-derived monocyte subpopulations from patients with chronic coronary occlusions (CTO) and tested for arteriogenesis. Whole-genome mRNA expression analyses were performed on these three monocyte subpopulations, namely: (1) unstimulated-, (2) 3 hours LPS-stimulated-, (3) monocyte-derived macrophages. Whole-genome mRNA expression analysis amongst others confirmed increased expression of IFNbeta-regulated genes in patients with insufficient coronary collateralization (collateral flow index (CFI) ≤0.37 “nonresponders”), compared with patients having sufficient collateralization (CFI>0.37 “responders”).
2008-12-01 | GSE13290 | GEO
Project description:MicroRNAs (miRNAs), a class of post-transcriptional gene expression regulators, have recently been detected in human body fluids, including peripheral blood plasma as extracellular nuclease resistant entities. However, the origin and function of extracellular circulating miRNA remain essentially unknown. Here, we confirmed that circulating mature miRNA in contrast to mRNA or snRNA is strikingly stable in blood plasma and cell culture media. Furthermore, we found that most miRNA in plasma and cell culture media completely passed through 0.22?µm filters but remained in the supernatant after ultracentrifugation at 110?000g indicating the non-vesicular origin of the extracellular miRNA. Furthermore, western blot immunoassay revealed that extracellular miRNA ultrafiltrated together with the 96?kDa Ago2 protein, a part of RNA-induced silencing complex. Moreover, miRNAs in both blood plasma and cell culture media co-immunoprecipited with anti-Ago2 antibody in a detergent free environment. This is the first study to show that extracellular miRNAs are predominantly exosomes/microvesicles free and are associated with Ago proteins. We hypothesize that extracellular miRNAs are in the most part by-products of dead cells that remain in extracellular space due to the high stability of the Ago2 protein and Ago2-miRNA complex. Nevertheless, our data does not reject the possibility that some miRNAs can be associated with exosomes.
| S-EPMC3167594 | biostudies-literature
Project description:ImportanceFew studies have investigated the association of long-term ambient ozone exposures with respiratory morbidity among individuals with a heavy smoking history.ObjectiveTo investigate the association of historical ozone exposure with risk of chronic obstructive pulmonary disease (COPD), computed tomography (CT) scan measures of respiratory disease, patient-reported outcomes, disease severity, and exacerbations in smokers with or at risk for COPD.Design, setting, and participantsThis multicenter cross-sectional study, conducted from November 1, 2010, to July 31, 2018, obtained data from the Air Pollution Study, an ancillary study of SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study). Data analyzed were from participants enrolled at 7 (New York City, New York; Baltimore, Maryland; Los Angeles, California; Ann Arbor, Michigan; San Francisco, California; Salt Lake City, Utah; and Winston-Salem, North Carolina) of the 12 SPIROMICS clinical sites. Included participants had historical ozone exposure data (n = 1874), were either current or former smokers (≥20 pack-years), were with or without COPD, and were aged 40 to 80 years at baseline. Healthy persons with a smoking history of 1 or more pack-years were excluded from the present analysis.ExposuresThe 10-year mean historical ambient ozone concentration at participants' residences estimated by cohort-specific spatiotemporal modeling.Main outcomes and measuresSpirometry-confirmed COPD, chronic bronchitis diagnosis, CT scan measures (emphysema, air trapping, and airway wall thickness), 6-minute walk test, modified Medical Research Council (mMRC) Dyspnea Scale, COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), postbronchodilator forced expiratory volume in the first second of expiration (FEV1) % predicted, and self-report of exacerbations in the 12 months before SPIROMICS enrollment, adjusted for demographics, smoking, and job exposure.ResultsA total of 1874 SPIROMICS participants were analyzed (mean [SD] age, 64.5 [8.8] years; 1479 [78.9%] white; and 1013 [54.1%] male). In adjusted analysis, a 5-ppb (parts per billion) increase in ozone concentration was associated with a greater percentage of emphysema (β = 0.94; 95% CI, 0.25-1.64; P = .007) and percentage of air trapping (β = 1.60; 95% CI, 0.16-3.04; P = .03); worse scores for the mMRC Dyspnea Scale (β = 0.10; 95% CI, 0.03-0.17; P = .008), CAT (β = 0.65; 95% CI, 0.05-1.26; P = .04), and SGRQ (β = 1.47; 95% CI, 0.01-2.93; P = .048); lower FEV1% predicted value (β = -2.50; 95% CI, -4.42 to -0.59; P = .01); and higher odds of any exacerbation (odds ratio [OR], 1.37; 95% CI, 1.12-1.66; P = .002) and severe exacerbation (OR, 1.37; 95% CI, 1.07-1.76; P = .01). No association was found between historical ozone exposure and chronic bronchitis, COPD, airway wall thickness, or 6-minute walk test result.Conclusions and relevanceThis study found that long-term historical ozone exposure was associated with reduced lung function, greater emphysema and air trapping on CT scan, worse patient-reported outcomes, and increased respiratory exacerbations for individuals with a history of heavy smoking. The association between ozone exposure and adverse respiratory outcomes suggests the need for continued reevaluation of ambient pollution standards that are designed to protect the most vulnerable members of the US population.
| S-EPMC6902160 | biostudies-literature