Stephanus Van Eeden

Professor

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Graduate Student Supervision

Doctoral Student Supervision (Jan 2008 - Nov 2019)
Impact of diesel exhaust inhalation on the heart and blood vessels (2012)

Numerous epidemiological studies have shown that exposure to ambient particulate matter (PM) is implicated in increased cardiovascular morbidity and mortality; however, the biological mechanisms are not fully understood. Diesel exhaust (DE) is the single biggest contributor to the urban ambient PM, and accounts for up to 90% of the total mass of fine particulate mass in ambient air of many major cities, such as London. In this dissertation, I evaluated the effects of DE inhalation at an environmentally relevant level in a mouse model of atherosclerosis, the apolipoprotein E deficient (apoE knockout) mouse. I hypothesized that exposure to DE causes progression of atherosclerosis and vascular dysfunction, which leads to cardiovascular morbidity and mortality. I used a morphometric analysis to determine the compositional changes in atherosclerotic plaques, and showed that DE inhalation increased lipid accumulation, foam cell formation and smooth muscle cell recruitment in plaques, whereby suggesting a progression of atherogenesis. The magnitude of DE deposition in the lung correlates with foam cell formation suggesting a strong link between DE inhalation and atherogenesis. Oxidative stress markers, including CD36 and nitrotyrosine, were all increased after exposure to DE, suggesting that reactive oxygen species played an important role in this vascular effect. In addition, I showed that exposure to DE up-regulated iNOS and COX2 expression at both protein and mRNA levels in blood vessel and heart tissue. A functional study of blood vessels showed no impairment of acetylcholine (ACh) relaxation, but the sodium nitroprusside-stimulated endothelium-independent relaxation was enhanced following DE exposure. This could be partly explained by an increase in soluble guanylate cyclase expression in blood vessels. However, there was attenuated phenylephrine (PE)-stimulated vasoconstriction induced by DE exposure. An increased iNOS-derived NO production and up-regulation of COX2 could contribute to this attenuated constriction.In conclusion, I demonstrate that DE inhalation alters the composition of atherosclerotic plaque resulting in unstable plaques that are vulnerable to rupture. Oxidative stress and iNOS up-regulation contribute to these DE exposure-induced vascular effects. We postulate that compensatory effects are activated to minimize the deleterious impact of DE exposure on vascular function.

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Prospective Student Info Sessions

Faculty of Medicine Information Session

Date: Tuesday, 08 December 2020
Time: 11:00 to 12:00
UBC’s Faculty of Medicine is a global leader in both the science and the practice of medicine, and is home to more than 1,700 graduate students across over 20 graduate programs. In this session hosted by Dr Michael Hunt, Associate Dean, Graduate and Postdoctoral Education, we’ll provide an overview of the diverse array of graduate programs available, including cutting-edge research experiences in the biosciences, globally recognized population health education, quality health professional training, as well as certificate and online training options. Dr Hunt will also be joined by program advisors from across the faculty to take an inside look at the application process and provide some application tips to help make your application as strong as possible.
 
 

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