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dc.contributor.authorZhong, Jiaen_US
dc.contributor.authorColicino, Elenaen_US
dc.contributor.authorLin, Xinyien_US
dc.contributor.authorMehta, Amaren_US
dc.contributor.authorKloog, Itaien_US
dc.contributor.authorZanobetti, Antonellaen_US
dc.contributor.authorByun, Hyang‐Minen_US
dc.contributor.authorBind, Marie‐Abèleen_US
dc.contributor.authorCantone, Lauraen_US
dc.contributor.authorPrada, Diddieren_US
dc.contributor.authorTarantini, Letiziaen_US
dc.contributor.authorTrevisi, Letiziaen_US
dc.contributor.authorSparrow, Daviden_US
dc.contributor.authorVokonas, Pantelen_US
dc.contributor.authorSchwartz, Joelen_US
dc.contributor.authorBaccarelli, Andrea A.en_US
dc.date.accessioned2015-03-02T17:37:54Z
dc.date.issued2015en_US
dc.identifier.citationZhong, J., E. Colicino, X. Lin, A. Mehta, I. Kloog, A. Zanobetti, H. Byun, et al. 2015. “Cardiac Autonomic Dysfunction: Particulate Air Pollution Effects Are Modulated by Epigenetic Immunoregulation of Toll‐like Receptor 2 and Dietary Flavonoid Intake.” Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease 4 (1): e001423. doi:10.1161/JAHA.114.001423. http://dx.doi.org/10.1161/JAHA.114.001423.en
dc.identifier.issn2047-9980en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:14065362
dc.description.abstractBackground: Short‐term fine particles (PM2.5) exposure is associated with reduced heart rate variability, a strong predictor of cardiac mortality among older people. Identifying modifiable factors that confer susceptibility is essential for intervention. We evaluated whether Toll‐like receptor 2 (TLR2) methylation, a reversible immune‐epigenetic process, and its dietary modulation by flavonoids and methyl nutrients, modify susceptibility to heart rate variability effects following PM2.5 exposure. Methods and Results: We measured heart rate variability and PM2.5 repeatedly over 11 years (1275 total observations) among 573 elderly men from the Normative Aging Study. Blood TLR2 methylation was analyzed using pyrosequencing. Daily flavonoid and methyl nutrients intakes were assessed through the Food Frequency Questionnaire (FFQ). Every 10 μg/m3 increase in 48‐hour PM2.5 moving average was associated with 7.74% (95% CI: −1.21% to 15.90%; P=0.09), 7.46% (95% CI: 0.99% to 13.50%; P=0.02), 14.18% (95% CI: 1.14% to 25.49%; P=0.03), and 12.94% (95% CI: −2.36% to 25.96%; P=0.09) reductions in root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency power, and high‐frequency power, respectively. Higher TLR2 methylation exacerbated the root mean square of successive differences, standard deviation of normal‐to‐normal intervals, low‐frequency, and high‐frequency reductions associated with heightened PM2.5 (Pinteraction=0.006, 0.03, 0.05, 0.04, respectively). Every interquartile‐range increase in flavonoid intake was associated with 5.09% reduction in mean TLR2 methylation (95% CI: 0.12% to 10.06%; P=0.05) and counteracted the effects of PM2.5 on low frequency (Pinteraction=0.05). No significant effect of methyl nutrients on TLR2 methylation was observed. Conclusions: Higher TLR2 methylation may confer susceptibility to adverse cardiac autonomic effects of PM2.5 exposure in older individuals. Higher flavonoid intake may attenuate these effects, possibly by decreasing TLR2 methylation.en
dc.language.isoen_USen
dc.publisherBlackwell Publishing Ltden
dc.relation.isversionofdoi:10.1161/JAHA.114.001423en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4330067/pdf/en
dash.licenseLAAen_US
dc.subjectEpidemiologyen
dc.subjectepidemiologyen
dc.subjectepigeneticsen
dc.subjectheart rate variabilityen
dc.subjectinflammationen
dc.subjectnutritionen
dc.titleCardiac Autonomic Dysfunction: Particulate Air Pollution Effects Are Modulated by Epigenetic Immunoregulation of Toll‐like Receptor 2 and Dietary Flavonoid Intakeen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalJournal of the American Heart Association: Cardiovascular and Cerebrovascular Diseaseen
dash.depositing.authorZhong, Jiaen_US
dc.date.available2015-03-02T17:37:54Z
dc.identifier.doi10.1161/JAHA.114.001423*
dash.authorsorderedfalse
dash.contributor.affiliatedZhong, Jia
dash.contributor.affiliatedColicino, Elena
dash.contributor.affiliatedZanobetti, Antonella
dash.contributor.affiliatedMehta, A
dash.contributor.affiliatedTrevisi, Letizia
dash.contributor.affiliatedBaccarelli, Andrea
dash.contributor.affiliatedSchwartz, Joel
dc.identifier.orcid0000-0002-0464-3754
dc.identifier.orcid0000-0002-3436-0640
dc.identifier.orcid0000-0002-2557-150X


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