Effects of Particulate Matter on Insulin Resistance and Endothelial Progenitor Cells
Exposure to ambient air pollution is one of the leading causes of death world-wide. Many studies have shown that exposure to ambient fine particulate matter (PM2.5) increases the risk of cardiovascular disease (CVD), type 2 diabetes (T2D) and cardiovascular mortality in susceptible individuals. Nevertheless, the pathophysiology underlying these effects remains elusive.
We found that exposure of mice to concentrated PM2.5 (CAP) induces vascular inflammation, decreases vascular insulin/VEGF sensitivity and circulating endothelial progenitor cells (EPCs), and exacerbates systemic insulin resistance in mice fed an high fat diet. Treatment with, insulin sensitizer or antioxidants and pulmonary overexpression of extracellular superoxide dismutase (ecSOD) protected against the vascular effects of PM2.5.
Our ongoing research focuses on determining:
- How PM2.5 induces vascular insulin resistance and inflammation?
- How PM2.5-induced vascular insulin resistance and inflammation contribute to the development and progression of T2D and CVD?
- How vascular insulin signaling contributes to changes in EPC homeostasis after PM2.5 exposure and in diet-induced obesity?
- Which susceptible states predispose individuals to PM2.5 toxicity (e.g., diet-induced obesity, circadian dyssynchrony)?
- Which PM2.5 constituents and characteristics contribute to PM2.5 toxicity?
To answer these questions we utilize our inhalation exposure system (Versatile Aerosol Concentration Enrichment System, VACES), mouse models of diet-induced obesity and circadian dyssynchrony, and mice transgenic for e.g., ecSOD and eNOS.
Completion of our studies will identify novel mechanism(s) that contribute to vascular toxicity and the progression of cardiometabolic disease due to PM2.5 exposure that could help to develop methods to prevent and intervene vascular and cardiometabolic harm after PM2.5 exposure. We will uncover new susceptibility states and assess how the dose, timing, and constituents of PM2.5 affect vascular and cardiometabolic process, which is critically important in developing evidence-based regulation of ambient PM2.5 levels.
- Diploma (M.S. equivalent): Biochemistry, Ruhr University Bochum, Bochum, Germany. Diploma Thesis: "Function of the juxtamembrane-region of the Low Affinity Neurothrophine Receptor p75LNTR"
- Ph.D.: Institute of Environmental Medical Research (IUF) at the Heinrich-Heine University Düsseldorf, Düsseldorf, Germany. Doctoral Thesis: "Mechanisms and consequences of particle uptake in alveolar macrophages. Role of the actin cytoskeleton and the Fcγ-receptor-II"
- Postdoctoral Fellow: University of Louisville, Louisville, KY, USA
Effects of exposures to fine particulate matter and volatile air pollutants as well as obesity on EPC levels and function
Endothelial health and vascular resistance to insulin and VEGF
Changes leading to the progression of the vascular complications and the metabolic syndrome