Grant: CIHR Fellowship

The inhalation of toxic environmental particles (either cigarette smoke or air pollutants) is a worldwide public health problem. Epidemiological studies have shown that exposure to these articulate matter (particles smaller than 10 µm or PM10), are associated with lung and cardiovascular disease. Exposure to ambient PM causes lung inflammation and retention of these particles in the lung is thought to perpetuate lung tissue inflammatory responses, contributing to the development and exacerbation of chronic lung diseases such as asthma and COPD. We have made the novel observation that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) suppress the PM-induced lung inflammatory response in vivo, which is thought to be due to their anti-inflammatory or pleiotropic effects. We postulate that one of the potential mechanisms of how statins reduce lung inflammation could be through the processing and clearance of PM in the lung. We hypothesize that statins enhance the processing of PM in the lung and promote their removal from lung tissues to regional lymph nodes, thereby reducing both the local (lung) and systemic inflammatory responses induced by air pollution exposure. The main goal of my studies will be to determine the mechanisms how PM are processed by different lung cells, focusing on lung macrophages and how treatment with statins impact these properties. We will also determine the impact of statins on the pro-inflammatory mediators produced by lung cells that phagocytose PM and the downstream effect on the local (lung) and systemic inflammatory responses. These studies will involve an array of in vitro and in vivo studies, using our well established rabbit model of urban PM exposure. We expect these studies will reveal novel pathways that can be targeted in the future with therapies to prevent the respiratory and cardiovascular adverse health effects in high-risk individuals expose to a polluted environment.