Susceptibility to Libby Amphibole Induced Pulmonary Disease in the Cardiovascular Compromised Subpopulation

 

Trainee:

Jonathan Shannahan

Shannahan

Research Mentor:

Dr. Urmila Kodavanti, PhD

Kodavanti

Clinical Co-Mentor;

Dr. Andrew Ghio, MD

ghio
Project Description:

Subpopulations of people suffering from a variety of chronic diseases have demonstrated increased susceptibility to many types of air pollutants. Specifically those with underlying cardiovascular disease (CVD) have been shown to be sensitive to many inhaled toxicants such as tobacco smoke, sulfur dioxide, and particulate matter. This growing population of people existing with CVD has never been studied for enhanced susceptibility to asbestos-induced disease.

I hypothesize that the pulmonary system of these individuals will exhibit enhanced toxicity to asbestos due to a dysregulation of iron homeostasis associated with their underlying CVD. This dysregulation of iron homeostasis will contribute to an environment of oxidative stress in their lungs leading to an increased inflammatory response. I propose to address these hypotheses by using rat models of human CVD with known abnormalities in heme metabolism.

My first objective is to characterize the underlying pulmonary disease states of these models in order to understand the baseline levels of inflammation, oxidative stress, and dysregulation of iron. Then these models will be tested for their differential susceptibility to asbestos-induced injury focusing on the role of the labile iron pool in modulating oxidative stress and inflammation. These finding will then be translated to collected human lung biopsy samples.

Finally, I hope to investigate the mechanism of enhanced susceptibility and inflammation an interventional treatment with an iron chelator, reactive oxygen species scavenger, or antioxidant. Overall my project should provide insight into the mechanisms of pulmonary disease susceptibility associated with people suffering from CVD.