Open AccessCardiac Autonomic Dysfunction: Particulate Air Pollution Effects Are Modulated by Epigenetic Immunoregulation of Toll‐like Receptor 2 and Dietary Flavonoid Intake
Author(s) -
Zhong Jia,
Colicino Elena,
Lin Xinyi,
Mehta Amar,
Kloog Itai,
Zanobetti Antonella,
Byun HyangMin,
Bind MarieAbèle,
Cantone Laura,
Prada Diddier,
Tarantini Letizia,
Trevisi Letizia,
Sparrow David,
Vokonas Pantel,
Schwartz Joel,
Baccarelli Andrea A.
Publication year - 2015
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.114.001423
Subject(s) - medicine , heart rate variability , interquartile range , heart rate , nutrient , endocrinology , physiology , blood pressure , biology , ecology
Background 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 ( TLR 2 ) 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. Methods and Results 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 TLR 2 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 TLR 2 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 PM 2.5 ( 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 TLR 2 methylation (95% CI : 0.12% to 10.06%; P =0.05) and counteracted the effects of PM 2.5 on low frequency ( P interaction =0.05). No significant effect of methyl nutrients on TLR 2 methylation was observed. Conclusions Higher TLR 2 methylation may confer susceptibility to adverse cardiac autonomic effects of PM 2.5 exposure in older individuals. Higher flavonoid intake may attenuate these effects, possibly by decreasing TLR 2 methylation.