Baylor Researchers Awarded NIH Funding to Study Thoracic Aortic Aneurysm, Dissection and Rupture

The research team including Dr. Ying Shen, professor of surgery and director of the Aortic Disease Research Lab; Dr. Scott LeMaire, professor of and vice chair for research in the Department of Surgery; and Dr. Ketan Ghaghada, associate professor of radiology at Baylor College of Medicine and manager of the Basic Science Research Program at Texas Children’s Hospital, have been awarded an NIH R01 grant from the NHLBI totaling over $2.6 million during their four-year funding segment for their project, “Endothelial Dysfunction in the Development of Aortic Degeneration, Dissection, and Rupture.”

In this project the team is investigating the factors in the progression of ascending thoracic aortic aneurysms and dissections (ATAAD). These diseases are often deadly but little is known about the underlying factors in the progression of them.

Researchers plan to:

1. Investigate the role of endothelial necroptosis/pyroptosis in ATAAD development
2. Study the mechanisms underlying necroptosis/pyroptosis induction
3. Test the therapeutic effects of blocking necroptosis/pyroptosis in preventing endothelial injury and ATAAD development

Multiple state-of-art technologies including endothelial cell specific knocking down of necroptosis/pyroptosis molecules in mice, single-cell transcriptomics, single-cell epigenomics, and nanoparticle contrast-enhanced CT imaging will be used to achieve these goals.
Dr. Shen, Dr. LeMaire and Dr. Ghaghada expect that the studies will provide insight which will in turn enable development of treatments for preventing disease progression and its often fatal outcome.

Preliminary studies from the researchers suggest a critical role of endothelial cell injury and barrier dysfunction in the initiation of ATAAD development. They have observed profound induction of necroptosis and pyroptosis, two important types of programmed necrotic cell death, in endothelial cells in the early stage of ATAAD development. Endothelial cell injury and subsequent hyperpermeability caused blood component infiltration, interlaminar space expansion, elastic fiber delamination, and microdissection.