Research Highlight: DNA Hypomethylation, Ambient Particulate Matter, and Increased Blood Pressure

AM Rush Hour In Beijing by Scott MeltzerAir pollution continues to be a major worldwide public health concern. Although substantial efforts to control emissions in the past decades have reduced air pollution, unhealthy levels of particulate matter (PM) and traffic pollution are not uncommon in most large cities.  Historically, exceptionally high levels of PM pollution have been followed by increased hospitalization and death from cardiovascular disease.

Understanding the mechanisms linking air pollution exposure to these deadly cardiovascular outcomes is critical to preventing and treating them, and is the goal of an international research team led by investigators at the Harvard School of Public Health and the Channing Laboratory of the Brigham and Women’s Hospital.

Blood pressure (BP), can change rapidly in response to many environmental stressors, including exposure to air pollution. Even small increases in systolic BP are estimated to increase the risk of Cardiovascular Disease (CVD) substantially, and trigger cardiovascular events. Changes in BP may be the key link between PM air pollution and CVD.

Airborne particles can be inhaled and deposited in the upper and lower airways. Because of their smaller size, fine particles can reach more deeply into the lungs, and are thought to have more harmful effects on the CV system. Exposure to fine particulate-matter air pollution has been related to increases in BP in humans. However, whether exposure to coarse PM also increases BP has not been studied.

The mechanism by which PM causes increased BP is also uncertain. Recent observational studies have linked PM exposures with blood DNA hypomethylation, a change in DNA molecules that can make the body less able to suppress inflammatory and vascular responses. Reduced methylation of DNA in blood has been noted in patients with CVD and with related conditions and risk factors, but until now, there was no experimental evidence to validate these observations and demonstrate a relationship between PM, hypomethylation, and BP.

The researchers, including Center Members Andrea Baccarelli and Diane Gold, conducted a study of human exposure to concentrated ambient particles (CAPs), including both fine and course PM. Fifteen healthy adult participants were exposed for 130 minutes to fine CAPs, coarse CAPs, or filtered medical air (control) in randomized order with at least a 2-week washout period in between exposures.

The researchers measured BP and DNA methylation from blood samples before and after each exposure.  They were able to demonstrate, for the first time, that both course and fine PM lowered blood methylation and increased systolic BP, and that decreased methylation was associated with higher systolic as well as diastolic BP.

These findings provide novel evidence of effects of coarse PM on BP, and confirm effects of fine PM. They also, provide the first experimental evidence of PM-induced DNA hypomethylation and its correlation to BP.

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DNA hypomethylation, ambient particulate matter, and increased blood pressure: findings from controlled human exposure experiments.

Bellavia A, Urch B, Speck M, Brook RD, Scott JA, Albetti B, Behbod B, North M, Valeri L, Bertazzi PA, Silverman F, Gold D, A Baccarelli A.,  J Am Heart Assoc. 2013 Jun 19;2(3):e000212.

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