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  • Ovid Technologies (Wolters Kluwer Health)  (3)
  • Liang, Liming  (3)
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  • Ovid Technologies (Wolters Kluwer Health)  (3)
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  • 1
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Circulation Research Vol. 120, No. 11 ( 2017-05-26), p. 1754-1767
    In: Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 120, No. 11 ( 2017-05-26), p. 1754-1767
    Abstract: Acute coronary syndrome (ACS) is a leading cause of death worldwide. Immune functions play a vital role in ACS development; however, whether epigenetic modulation contributes to the regulation of blood immune cells in this disease has not been investigated. Objective: We conducted an epigenome-wide analysis with circulating immune cells to identify differentially methylated genes in ACS. Methods and Results: We examined genome-wide methylation of whole blood in 102 ACS patients and 101 controls using HumanMethylation450 array, and externally replicated significant discoveries in 100 patients and 102 controls. For the replicated loci, we further analyzed their association with ACS in 6 purified leukocyte subsets, their correlation with the expressions of annotated genes, and their association with cardiovascular traits/risk factors. We found novel and reproducible association of ACS with blood methylation at 47 cytosine-phosphoguanine sites (discovery: false discovery rate 〈 0.005; replication: Bonferroni corrected P 〈 0.05). The association of methylation levels at these cytosine-phosphoguanine sites with ACS was further validated in at least 1 of the 6 leukocyte subsets, with predominant contributions from CD8 + T cells, CD4 + T cells, and B cells. Blood methylation of 26 replicated cytosine-phosphoguanine sites showed significant correlation with expressions of annotated genes (including IL6R , FASLG , and CCL18 ; P 〈 5.9×10 −4 ), and differential gene expression in case versus controls corroborated the observed differential methylation. The replicated loci suggested a role in ACS-relevant functions including chemotaxis, coronary thrombosis, and T-cell–mediated cytotoxicity. Functional analysis using the top ACS-associated methylation loci in purified T and B cells revealed vital pathways related to atherogenic signaling and adaptive immune response. Furthermore, we observed a significant enrichment of the replicated cytosine-phosphoguanine sites associated with smoking and low-density lipoprotein cholesterol ( P enrichment ≤1×10 −5 ). Conclusions: Our study identified novel blood methylation alterations associated with ACS and provided potential clinical biomarkers and therapeutic targets. Our results may suggest that immune signaling and cellular functions might be regulated at an epigenetic level in ACS.
    Type of Medium: Online Resource
    ISSN: 0009-7330 , 1524-4571
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 1467838-X
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 50, No. 7 ( 2019-07), p. 1661-1668
    Abstract: Circulating metals synchronously reflect multiple metal exposures from both natural and anthropogenic sources, which may be linked with the risk of stroke. However, there is a lack of prospective studies investigating the associations of multiple metal exposures with incident stroke. Methods— We performed a nested case-control study within the ongoing Dongfeng-Tongji cohort launched in 2008. A total of 1304 incident stroke cases (1035 ischemic strokes and 269 hemorrhagic strokes) were prospectively identified by December 31, 2016, and matched to incident identity sampled controls according to age (within 1 year), sex, and blood sampling date (within 1 month). We determined the concentrations of 24 plasma metals and assessed the associations of plasma multiple metal concentrations with incident stroke using conditional logistic regression and elastic net model. Results— The average follow-up was 6.1 years. After adjusting for established risk confounders, copper, molybdenum, and titanium were significantly associated with higher risk of ischemic stroke (odds ratios according to per interquartile range increase, 1.29 [95% CI, 1.13–1.46], 1.19 [95% CI, 1.05–1.35] , and 1.30 [95% CI, 1.07–1.59]), whereas rubidium and selenium were associated with lower risk of hemorrhagic stroke (odds ratios according to per interquartile range increase, 0.66 [95% CI, 0.50–0.87] and 0.68 [95% CI, 0.51–0.91]). The predictive plasma metal scores based on multiple metal exposures were significantly associated with higher risk of ischemic and hemorrhagic stroke (adjusted odds ratios according to per interquartile range increase, 1.37 [95% CI, 1.20–1.56] and 1.53 [95% CI, 1.16–2.01]). Conclusions— Plasma copper, molybdenum, and titanium were associated with higher risk of ischemic stroke, whereas plasma rubidium and selenium were associated with lower risk of hemorrhagic stroke. These findings may have important public health implications given the ever-increasing burden of stroke worldwide.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Journal of the American Heart Association Vol. 10, No. 6 ( 2021-03-16)
    In: Journal of the American Heart Association, Ovid Technologies (Wolters Kluwer Health), Vol. 10, No. 6 ( 2021-03-16)
    Abstract: Mounting evidence suggests that circulating microRNAs (miRNAs) are critical indicators of cardiovascular disease. However, prospective studies linking circulating miRNAs to incident acute coronary syndrome (ACS) are limited, and the underlying effect of associated miRNA on incident ACS remains unknown. Methods and Results Based on a 2‐stage prospective nested case–control design within the Dongfeng‐Tongji cohort, we profiled plasma miRNAs from 23 pairs of incident ACS cases and controls by microarray and validated the candidate miRNAs in 572 incident ACS case–control pairs using quantitative real‐time polymerase chain reaction. We observed that plasma miR‐4286 was associated with higher risk of ACS (adjusted odds ratio according to an interquartile range increase, 1.26 [95% CI, 1.07–1.48]). Further association analysis revealed that triglyceride was positively associated with plasma miR‐4286, and an interquartile range increase in triglyceride was associated with an 11.04% (95% CI, 3.77%–18.83%) increase in plasma miR‐4286. In addition, the Mendelian randomization analysis suggested a potential causal effect of triglyceride on plasma miR‐4286 ( β coefficients: 0.27 [95% CI, 0.01–0.53] and 0.27 [95% CI, 0.07–0.47] separately by inverse variance‐weighted and Mendelian randomization‐pleiotropy residual sum and outlier tests). Moreover, the causal mediation analysis indicated that plasma miR‐4286 explained 5.5% (95% CI, 0.7%–17.0%) of the association of triglyceride with incident ACS. Conclusions Higher level of plasma miR‐4286 was associated with an increased risk of ACS. The upregulated miR‐4286 in plasma can be attributed to higher triglyceride level and may mediate the effect of triglyceride on incident ACS.
    Type of Medium: Online Resource
    ISSN: 2047-9980
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2653953-6
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