Pulmonary arterial hypertension, or PAH, is a rare and life-threatening condition characterized by high blood pressure in the arteries of the lungs. Blood vessels in the lungs of patients with PAH exhibit excess inflammation, which is thought to contribute to disease development.
Department of Medicine Professor Ankit A. Desai, MD, along with Tae-Hwi L. Schwantes-An, PhD, an assistant professor in the Department of Medical and Molecular Genetics, were part of the research team, which recently published their findings in Science.
In the study, researchers outlined their discovery that a gene called NCOA7 “acts as a biological brake on inflammation in the lining of blood vessels.” Deficiency in the NCOA7 gene directly contributes to inflammation of the blood vessels by altering lysosomal function and cholesterol metabolism, which then exacerbates pulmonary hypertension, Desai said.
The researchers also found that both abnormal cholesterol metabolite levels and variation in the NCOA7 gene were associated with increased risk of death.
They developed a chemical compound that augmented NCOA7 function. Activating the gene, researchers found, improved PAH disease manifestations.
The study was led by Stephen Chan, MD, PhD, from the University of Pittsburgh, and was supported, in part, by Desai’s R01 grant from the National Institutes of Health.
Desai is a member of the Division of Cardiovascular Medicine in the Department of Medicine, and he is the associate cardiovascular fellowship program director for research. His research interests include sickle cell disease and pulmonary hypertension, and his clinical activity is focused on caring for patients who suffer from these diseases and heart failure.
Schwantes-An's research focuses on understanding the genetic underpinnings of complex diseases such as PAH, substance use disorders and neuro-developmental and behavioral diseases.
