Exposure to ambient air pollution has been linked to annually 7 million premature deaths worldwide and 200,000 in the US and the global burden of air pollution is likely to increase due to increasing urbanization and industrialization. Extensive research has shown that exposure to particulate air pollution and specifically fine particulates (PM2.5) increase the risk of cardiovascular disease and diabetes. However, despite this extensive evidence, it is unclear how PM2.5 exposure increases the cardiometabolic risk and which susceptible states increase the sensitivity to vascular and cardiometabolic injury due to PM2.5 exposure. In our proposed studies we attempt to disentangle the mechanism leading to the toxicity of PM2.5 by testing the novel hypothesis that PM2.5 disrupts vascular circadian rhythms and that this contributes to the development of cardiometabolic disease in a new susceptibility state of circadian dyssynchrony. This hypothesis is supported by our preliminary data showing that that exposure to concentrated ambient PM2.5 (CAP) alters the rhythmic expression of clock genes in the murine aorta and increases insulin resistance in mice with the disturbed light/dark cycle (circadian dyssynchrony). As this models a real-world scenario in which individuals with disturbed light cycle (e.g. due to light pollution, sleep deprivation) are exposed to air pollution it is of high relevance to our modern urban 24 h lifestyle associated with air and light pollution and changes in sleep behavior. Successful completion of this project will identify new targets of and novel susceptibility states (circadian dyssynchrony and chronotoxicity) for PM2.5 toxicity. Results of theses studies will be of significance in understanding the adverse health effects originated from our modern lifestyle and could ultimately lead to the development of evidence-based guidelines and policies to minimize the cardiometabolic effects of urbanization and pollutant exposure.
Goal of this project is to test the novel hypothesis that air pollution exposure, a major health concern worldwide that increase the risk of cardiovascular disease and diabetes, disrupts vascular circadian rhythms and that this exacerbates cardiometabolic injury in the new susceptibility state of circadian dyssynchrony. Results of this project will be of significance in understanding and preventing the adverse health effects originated from air pollution exposure.