Background and Objectives: Ambient particulate matter (PM) in real urban air pollution (RUA) is an environmental health risk factor associated with increased cardiac events. This study investigated the threshold level to induce arrhythmia, as well as arrhythmogenic mechanism of RUA that mainly consisted of PM <2.5 μm in aerodynamic diameter close to ultrafine particles. Methods: RUA was artificially produced by a lately developed pyrolysis based RUA generator. C57BL/6 mice were divided into 4 groups: a control group (control, n=12) and three groups with exposure to RUA with the concentration of 200 µg/m3 (n=12), 400 µg/m3 (n=12), and 800 µg/m3 (n=12). Mice were exposed to RUA at each concentration for 8 hr/day and 5 day/week to mimic ordinary human activity during 3 weeks. Results: The QRS and QTc intervals, as well as intracellular Ca2+ duration, apicobasal action potential duration (APD) gradient, fibrosis, and inflammation of left ventricle of mouse hearts were increased dose-dependently with the increase of RUA concentration, and significantly increased at RUA concentration of 400 µg/m3 compared to control (all p<0.001). In mice exposed to RUA concentration of 800 µg/m3, spontaneous ventricular arrhythmia was observed in 42%, with significant increase of inflammatory markers, phosphorylated Ca2+/calmodulin-dependent protein kinase II (CaMKII), and phospholamban (PLB) compared to control. Conclusions: RUA could induce electrophysiological changes such as APD and QT prolongation, fibrosis, and inflammation dose-dependently, with significant increase of ventricular arrhythmia at the concentration of 400 µg/m3. RUA concentration of 800 µg/m3 increased phosphorylation of CaMKII and PLB.
Bibliographical noteFunding Information:
This study's protocol was supported by the Institutional Animal Care and Use Committee of Yonsei University (IACUC-201710-640-01), and conformed to the guideline for the care and use of laboratory animals published by the United States National Institutes of Health.
This study was supported by research grants from the Korean Cardiac Research Foundation (201803-01), the Basic Science Research Program through the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology (NRF-2017R1A2B3003303), and the Korean Healthcare Technology R&D project, which is funded by the Ministry of Health & Welfare (HI16C0058). The Hyewon Park was supported by RP-Grant 2020 of Ewha Womans University.
All Science Journal Classification (ASJC) codes
- Internal Medicine
- Cardiology and Cardiovascular Medicine