Drs. LeMaire and Shen Awarded NIH-NHLBI R01 Funding to Study Aortic Degeneration
Dr. Scott LeMaire, professor of surgery in the Division of Cardiothoracic Surgery and vice-chair for research, and Dr. Ying Shen, professor of surgery in the Division of Cardiothoracic Surgery and director of the Aortic Disease Research Lab, have been awarded an National Institute of Health R01 grant from the National Heart, Lung, and Blood Institute totaling over $2,400,000 during the initial four-year funding segment for his project titled, “Pro-inflammatory Pyroptotic Cell Death in Aortic Degeneration.”
The preliminary findings of this study suggest that damaged DNA in smooth muscle cells (SMC) activate a pore-forming protein, gasdermin D (GSDMD), that drives SMC pyroptosis, an inflammatory form of programmed cell death that can represent a common pathway to aortic SMC loss. The long-term goal of this study is to improve the understanding of the molecular pathogenesis of sporadic ascending thoracic aortic aneurysms and dissections in hope of developing new pharmacological strategies to prevent disease progression.
Dr. LeMaire’s and Dr. Shen’s basic science laboratory research—conducted in the Aortic Disease Research Lab—is currently focusing on the role of various aspects of extracellular matrix metabolism in the development of aortic aneurysms and dissections. In particular, his group is studying the roles of destructive factors, such as inflammatory cells and proteases, as well as reparative mechanisms, such as stem cell recruitment and transformation, during the development of aortic aneurysms and dissections. Their lab performed novel experiments demonstrating that ciprofloxacin, a commonly prescribed fluoroquinolone antibiotic, causes severe damage to the aortic wall in susceptible mice, supporting that these drugs should be avoided in patients with or at risk for aortic aneurysms or dissections.