In humans, large arteries lose elasticity and thicken with age and other pathological conditions, leading to arteriosclerosis and high blood pressure. Age-related arterial stiffening affects a large population and is a major risk factor for cardiovascular disease, yet it remains poorly understood, with no effective intervention.
Work being done in the lab of Zhongjie Sun, MD, PhD, FAHA, professor and chair of the UTHSC Department of Physiology, is focused on discovering the epigenetic causes of this condition. The National Institutes of Health is supporting these efforts, recently awarding Dr. Sun $2.25 million for his project, “Investigation into Arterial Stiffness and Hypertension.”
The study centers on the protein KDM6A, a recently discovered histone demethylase (an enzyme that controls the activity of certain genes by modifying specific proteins). Mutation of this gene causes severe defects in the formation and development of human embryos. The proposed research will investigate whether KDM6A in cells lining the blood vessel walls help regulate the elasticity and structural soundness of the arteries. It will also investigate whether KDM6A is involved in arterial stiffness and hypertension that occurs as we get older.
The idea that KDM6A is essential in maintaining normal arterial health is new, as is the technical approach being taken to prove this hypothesis. Dr. Sun’s lab will be using state-of-the-art techniques that allow temporary control of KDM6A at a given time-point in an animal model. This will enable the researchers to study the precise effects of inactivating the enzyme within certain cells.
“This grant will help us further explore why blood vessels get stiff in aged people,” said Dr. Sun, who is also the Thomas A. Gerwin Chair of Excellence in Physiology and co-director of the UT Methodist Cardiovascular Institute. “Our studies may lead to discovery of a new therapeutic target (KDM6A) for aging-related arterial stiffness.” Dr. Sun’s project is being funded for four years by the National Heart, Lung and Blood Institute.