Igor Zelko, PhD

Blocking Remodeling in Lung’s Blood Vessels in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a devastating disease; only about half of patients survive five years after diagnosis. The lung’s blood vessels are remodeled and constrict, leading to heart failure due to an enlarged and ineffective right side of the heart. Current drugs used to treat the disease enlarge the blood vessels, but do not block the eventual thickening of the artery walls and do not improve survival. More effective therapies are urgently needed.

“If it is successful, eventually this drug could be used in human trials to stop, or even reverse progression of the disease.”
With the assistance of an American Lung Association Biomedical Research Grant, Igor Zelko, PhD, is studying the mechanisms that regulate remodeling of blood vessel walls in the lung. He is focusing on a substance that inhibits an enzyme called histone deacetylase, which he hopes will provide clues that could lead to better therapy for PAH.

A process called acetylation, or modification of histones regulates the expression of a major antioxidant enzyme in the pulmonary arteries. Dr. Zelko is investigating whether histone deacetylase inhibitors will significantly elevate levels of this antioxidant enzyme, called extracellular superoxide dismutase, which in turn will reduce or completely block remodeling of the lung’s blood vessel walls and slow or prevent the development of PAH in a mouse model.

“If it is successful, eventually this drug could be used in human trials to stop, or even reverse progression of the disease,” Dr. Zelko says.

He is particularly grateful to the American Lung Association for funding his research. “My startup funding had ended, and if I had not received the American Lung Association grant, I could not have continued this research, which I have been working on for the last 10 years,” he said.