대기 미세먼지로 인한 심장 부정맥 발생 기전 규명

Abstract

Ambient particulate matter (PM) is a mixture of many different chemicals to which inorganic compounds including heavy metals and other organic compounds are attached. The chemical components of PM vary by their origin or source, and may cause the adverse effects on human health as well as environment. Recently, epidemiological studies have suggested that increased levels of PM is positively associated with cardiovascular morbidity and mortality such as arrhythmia, atherosclerosis, myocardial infarction, and myocardial hypertrophy. However, despite the concrete evidence of the cardiac development of PM, the underlying mechanism is still poorly understood. The main aim of this study was investigate to the arrhythmogenic effect of PM and to explore the possible mechanism of arrhythmogenic effect induced by PM in cardiomyocytes (CMCs). Ambient PM were collected in summer season (SS1) and winter season (SW1) in Seoul metropolitan area. For the arrhythmogenic effect of SS1 and SW1, primary CMCs were isolated from neonatal rat and exposed to SS1 and SW1 in different concentrations. Then, The resting membrane potential (RMP), heart rate and action potential amplitude (APA) in CMCs were recorded by single-cell patch-clamp techniques. Results showed that contraction and relaxation of CMCs were markedly altered by SS1 and SW1. For the possible mechanism of arrhythmogenic effect induced by SS1 and SW1, we measured intracellular calcium and reactive oxygen species (ROS) in CMCs using the indicators fluo-4am and H2DCF-DA, respectively. The mRNA , protein expression and phosphorylation status of key calcium homeostasis-related proteins such as RyR2 (ryanodine receptor2), SERCA2a (sarco/endoplasmic reticulum Ca2+ -ATPase), NCX (sodium-calcium exchanger), CaMKII (Ca2+/calmodulin-dependent protein kinase II); and phosphorylation activation of Akt and ERK1/2 were evaluated by qPCR and western blot assay. Results showed that the fluorescence of intracellular calcium and ROS increased in a concentration-dependent manner as compared to the control. Calcium homeostasis-related proteins, p-Akt and p-ERK1/2 also indicated the change in concentration-dependent manner by SS1 and SW1. Howevere these effects were prevented by pretreatement of CMCs with ROS scavenger N-acetylcysteine (NAC, 1mmol/L). In conclusion, our findings confirmed that PM has arrhythmogenic effect on CMCs via increased ROS and perturbed calcium handling. moreover, oxidative stress could be one of the major mechanisms of these arrhythmogenic effect.