Role of Endothelial Dysfunction as a Key Pathogenic Driver of Hypertrophic Cardiomyopathy
Abstract
Cardiomyopathy is a term describing diseases of the heart muscle, where the walls of the heart chambers have become stretched, thickened, or stiff, resulting in impairment of the heart’s ability to pump blood to the body. In hypertrophic cardiomyopathy (HCM), the heart muscle cells have enlarged and the walls of the heart chambers thicken. The chambers are reduced in size so they can t hold much blood, and the walls can t relax properly and may stiffen. As it is a genetic, inherited condition, it can occur in young, active males, including those serving in the active duty military, and will require continuous management after discharge from the service. Current treatment options manage the related arrhythmias to prevent sudden cardiac death, but do not offer any relief in the thickening of the heart muscle. The role of the endothelial cells, or the inner lining of the blood vessels including those in the heart, in development of HCM has not been defined. Our preliminary studies have demonstrated a compelling finding that disrupting the expression of the gene ERK5 specifically in the endothelial cells results in spontaneous HCM in mice, which succumb to death by 6 weeks after the gene is deleted. How the disruption of this gene results in the catastrophic thickening of the heart muscle and death remains to be determined. This project will investigate how the endothelial ERK5 gene regulated heart function and structure, and how we can target this gene and its downstream targets to develop new therapies for HCM.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810320
Entities
People
- Hyung J Chun
Organizations
- United States Army
- Yale University