Project title: Association Between In-Utero Exposure to Diesel Exhaust and N-acetyl-cysteine Supplementation in Hyperlipidemic Pregnant Mice and Development of Atherosclerosis at Multiple Vascular Sites in the Offspring
Completed in: 2016 | Faculty advisor: Michael E. Rosenfeld
Background: Cardiovascular disease is a leading cause of mortality in the world, accounting for an estimated 17.5 million deaths (WHO 2015 factsheet). Recent studies on the influence of environmental factors have shown an association between air pollution and heart disease, with diesel exhaust emission having a significant impact. Several mechanisms by which diesel particulate matter affect heart disease have been proposed, but the exact molecular mechanism involved remains unclear. This study was proposed to evaluate the association between in-utero exposure to diesel exhaust (DE) emission +/- maternal N-acetyl cysteine (NAC) supplementation and the development of atherosclerosis in the offspring later in life.
Methodology: In this study, pregnant hyperlipidemic apolipoproteinE (apoE -/-) deficient mice were randomized into one of four exposure groups: DN (DE + NAC), DC (DE + control water), FN (filtered air + NAC) and FC (filtered air + control water). The offspring born to these dams were nurtured in a controlled environment and sacrificed at 16 weeks of age. Various tissue specimens were isolated, including the innominate arteries (IA) which were examined microscopically for the presence of atherosclerotic lesions and morphological changes in the artery wall.
Results: Offspring born to DN dams recorded larger mean innominate atherosclerotic lesion areas and medial thickening. The prevalence of peri-adventitial fat in diesel exposed groups combined (DC and DN) was 1.49 times (95% CI 1.02-1.54) that of prevalence of peri-adventitial fat in the filtered air groups (FC and FN). No correlation was drawn between lesion development at the innominate artery versus the aortic sinus for a given exposure group. Lastly, an interesting trend which was observed was an increase in cumulative mortality between the 12th and 16th week for the DC group compared to the others.
Conclusion: The results obtained in this study suggest that in-utero diesel exhaust exposure is associated with peri-adventitial adipose tissue, but is largely not associated with vascular remodeling and atherosclerotic progression. More research is needed to better our understanding of the effect of environmental factors on ischemic heart disease and the role of protective agents in this disease process.