Global DNA Hypomethylation and Reduced Levels of Inflammatory Mediators Are Associated to High Air Pollution in a Prospective Cohort of Healthy Subjects

Fernando Lanas, Montserrat A Hevia, Isis Paez, Katherine Andara, Nicolás Saavedra, Kathleen Saavedra, Pamela Serón, Luis A Salazar

Abstract

Introduction: Temuco is located in Southern Chile and has elevated levels of air pollution (AP), mainly due to the use of wood as combustion throughout the cold season. Further, patients admitted for acute coronary syndrome (ACS) in the public hospital doubles during this period. There are evidences that AP produces changes in DNA methylation and that this epigenetic modification could be one of the mechanisms mediating systemic inflammation ending in ACS. Hypothesis: AP induces DNA methylation changes that modulate the expression of inflammatory mediators leading to an increased ACS incidence during high air pollution season in Temuco. Methods: 91 subjects (mean age 52.1 ± 10.5) without cardiovascular diseases were randomly selected from general population. We obtained demographic and clinical information during low (LP) and high (HP) air pollution season. Serum glucose, lipids and inflammatory proteins were measured by colorimetric methods and multiplex system. Blood leucocytes DNA was used to quantify global methylation using an ELISA-like assay. Analyses were performed using Wilcoxon matched-pairs signed rank test. Results: No differences were observed in weight, heart rate, diastolic blood pressure and serum glucose. Total and HDL cholesterol (LP/HP (mg/dL): 205.5 ± 38.4/193.7 ± 43.3; p=0.0014 and 58.7 ± 14.3/44.7 ± 13.1; p<0.0001), triglycerides (LP/HP (mg/dL): 168.3 ± 107.0/139.6 ± 83.8, p<0.0001) and waist-hip ratio (LP/HP: 0.93 ± 0.08/0.92 ± 0.07; p<0.0001) were significantly lower at HP season, while systolic blood pressure was significantly higher (LP/HP (mmHg): 127.3 ± 21.2/130.12 ± 23; p=0.04). Levels of circulating inflammatory proteins (LP/HP median (pg/ml) for MMP-1: 162.8/52.74; MMP-2: 902.3/272.9; MMP-9: 66.97/30.38; IL1-β: 0/0; IL-6: 17.08/13; IL-10: 3.581/2.754; IL-18: 63.64/35.63, sICAM: 208149/121654; sVCAM: 162.8/52.74; MCP-1: 162.2/55.81 and TNFα: 31.33/25.39; p<0.0001) and global DNA methylation (median 1.071/0.548%; p=0.0002) were significantly lower during HP. Conclusions: HP was associated with a DNA hypomethylation status and lower levels of acute inflammatory molecules, the latest is opposite with what has been reported. Future analyzes in ACS patients will help us to clarify this association.

Más información

Fecha de publicación: 2019
Año de Inicio/Término: November 16th-18th, 2019.