Do Nutrients Counteract the Acute Cardiovascular Effects of Air Particles? The Role of Immuno-Epigenetics in Observational and Intervention Studies

Abstract

Background: Fine particulate matter (PM2.5) pollution is a major risk factor for cardiovascular diseases. Identifying modifiable factors and preventative strategies to mitigate the cardiovascular effect of PM2.5 is essential to aid the development of personalized intervention. Method: Chapter one and two were based on a crossover human intervention trial using B vitamin supplementation (2.5 mg/d folic acid, 50 mg/d vitamin B6, and 1 mg/d vitamin B12). Ten volunteer received three two-hour controlled exposure experiments to medical air or PM2.5 (250μg/m3), in pre-determined order. Chapter three utilized the Normative Aging Study, a longitudinal cohort study with 573 elderly men. We used electrocardiogram to measure resting heart rate (HR) and heart rate variability (HRV), hematology analyzer to determine white blood cell (WBC) counts, and Infinium HumanMethylation450 BeadChip to measure DNA methylation in peripheral CD4+ T helper (Th) cells (pre-, post-, 24-hr post-exposure). Blood TLR2 methylation was analyzed using pyrosequencing. Daily flavonoid and methyl nutrients intakes were assessed through the Food Frequency Questionnaire. Results: Compared to medical air, PM2.5 exposure was associated with 3.8 beat/min (95% CI, 0.3, 7.4; P=0.04) higher resting HR, 57.5% (95% CI, 2.5%, 81.5%; P=0.04) lower low-frequency (LF) power, and altered DNA methylation landscape, following exposure. PM2.5 exposure was associated with 11.5% (95% CI, 0.3%, 24.0%; P=0.04) higher total WBC count and 12.9% (95% CI, 4.4%, 22.1%; P=0.005) higher lymphocyte count, at 24-hour post-exposure. These effects of PM2.5 were abrogated with B vitamins supplement. In the Normative Aging Study, every 10 µg/m3 increase in 48-hour PM2.5 moving average was associated with 7.74% (95%CI: -1.21%, 15.90%; P=0.09), 7.46% (95%CI: 0.99%, 13.50%; P=0.02), 14.18% (95%CI, 1.14%, 25.49%; P=0.03), and 12.94% (95%CI, -2.36%, 25.96%; P=0.09) reductions in root mean square of successive differences (rMSSD), standard deviation of normal-to-normal intervals (SDNN), LF power, and high-frequency (HF) power, respectively. Higher TLR2 methylation exacerbated the rMSSD, SDNN, LF, and HF 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%, 10.06%; P=0.05) and counteracted the effects of PM2.5 on LF (Pinteraction=0.05). Conclusions: Ambient PM2.5 exposure peak has unfavorable effect on cardiac autonomic function, the immune system, and the epigenome – which, can be counteracted by B vitamins supplementation. In addition, the epigenetic regulation of TLR2-related immunity may determine vulnerability of older individuals when confronted with air pollution peaks.