Imad Al Ghouleh, Ph.D.
University of Pittsburgh
Funded by the American Lung Association of the Upper Midwest
Studying Heart's Response to Pulmonary Arterial Hypertension
Pulmonary arterial hypertension (PAH) is a devastating disease where blood vessels in the lung undergo changes that result in resistance to blood flow. The heart responds by thickening its right ventricle (RV) to overcome this resistance. Eventually, these changes lead to RV failure, the leading cause of death from PAH. The presence of fluid, or effusion, in the sac surrounding the heart called the pericardium during PAH is predictive of increased mortality and RV failure. It is unclear what the link between PAH, pericardial effusions and RV failure is. We will study the mechanisms underlying these processes. We hope to gain insights that will lead to identifying new therapeutic targets to combat this deadly disease.
Update: This year we made significant progress toward understanding the molecular mechanisms underlying right ventricle hypertrophy in PAH. We conducted animal experiments in which we surgically constricted the size of the pulmonary artery to mimic the pressure increase the right ventricle experiences in PAH. We then studied the effects of different constrictions and duration of constriction on right ventricle responses in males and females, and found gender differences in the results. We also tested involvement of cellular pathways in these processes.
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