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PMID: 25628407 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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 ·Vol. 4 ·No. 1 ·2015-01-27 ·Pages e001423

Zhong J, Colicino E, Lin X, Mehta A, Kloog I, Zanobetti A, Byun HM, Bind MA, Cantone L, Prada D, Tarantini L, Trevisi L, Sparrow D, Vokonas P, Schwartz J, Baccarelli AA

Abstract

Short-term fine particles (PM(2.5)) 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 PM(2.5) exposure. We measured heart rate variability and PM(2.5) 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/m(3) increase in 48-hour PM(2.5) 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 (P(interaction)=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 (P(interaction)=0.05). No significant effect of methyl nutrients on TLR2 methylation was observed. 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.

Keywords
epidemiology epigenetics heart rate variability inflammation nutrition
MeSH Terms
Aged Aged, 80 and over Aging/genetics,physiology Autonomic Nervous System Diseases/epidemiology Bradycardia/epidemiology,physiopathology Cohort Studies Diet Epigenomics Flavonoids/administration & dosage Geriatric Assessment Heart Conduction System/physiopathology Humans Immunomodulation/genetics Male Methylation Particulate Matter/adverse effects Prognosis Prospective Studies Survival Rate Toll-Like Receptor 2/immunology,metabolism
Chemicals
Flavonoids Particulate Matter Toll-Like Receptor 2
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Zhong Jia
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Colicino Elena
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Lin Xinyi
Department of Biostatistics, Harvard School of Public Health, Boston, MA (X.L., M.A.B.) Singapore Institute for Clinical Sciences, Singapore (X.L.).
Mehta Amar
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Kloog Itai
Department of Geography and Environmental Development, Ben-Gurion University of the Negev, Beer Sheva, Israel (I.K.).
Zanobetti Antonella
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Byun Hyang-Min
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Bind Marie-Abèle
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.) Department of Biostatistics, Harvard School of Public Health, Boston, MA (X.L., M.A.B.).
Cantone Laura
Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy (L.C., L.T.).
Prada Diddier
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Tarantini Letizia
Center of Molecular and Genetic Epidemiology, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy (L.C., L.T.).
Trevisi Letizia
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Sparrow David
VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA (D.S., P.V.).
Vokonas Pantel
VA Normative Aging Study, Veterans Affairs Boston Healthcare System and the Department of Medicine, Boston University School of Medicine, Boston, MA (D.S., P.V.).
Schwartz Joel
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
Baccarelli Andrea A
Department of Environmental Health, Harvard School of Public Health, Boston, MA (J.Z., E.C., A.M., A.Z., H.M.B., M.A.B., D.P., L.T., J.S., A.A.B.).
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Article Info
Journal
Journal of the American Heart Association
Abbr.
J Am Heart Assoc
ISSN
2047-9980
DOI
10.1161/JAHA.114.001423
Published
2015-01-27
Epub
2015-00-27
Pages
e001423
Language
English
Region
England
NLM ID
101580524
PMCID
PMC4330067
Subset
IM
Grants
NIEHS NIH HHS · R01 ES015172 · United States
NIEHS NIH HHS · R01 ES021357 · United States
NIEHS NIH HHS · P30 ES000002 · United States
NIEHS NIH HHS · R01 ES021733 · United States
NIEHS NIH HHS · R01ES015172 · United States
NIEHS NIH HHS · P30ES000002 · United States
NIEHS NIH HHS · R01ES021357 · United States
NIEHS NIH HHS · R21 ES021895 · United States
NIEHS NIH HHS · R01ES021733 · United States
NIEHS NIH HHS · R21ES021895 · United States
Corrections
ErratumIn
PMID: 26819248
External Links
PubMed source DOI: 10.1161/JAHA.114.001423 PMC Full Text View journal details
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