The long-term goal of this research proposes to understand reactive oxygen species (ROS)-induced oxidative stress and inflammatory signaling mechanisms altering sarcomeric protein function and leading to heart failure and dilated cardiomyopathy following either ischemia-reperfusion injury or mutations in the MYBPC3 gene.
The development of acute and chronic heart failure (HF) has been associated with increased inflammation and oxidative stress. Oxidative stress results from imbalances between ROS and antioxidant reserves, which can lead to elevated cardiac remodeling and functional HF. Inflammation produced by oxidative stress has been indicated as causative of many chronic human diseases. Dilated cardiomyopathy has been identified as the chronic phase of an inflammatory disease of the myocardium. In 30 - 40% of dilated cardiomyopathy cases, endomyocardial biopsy reveals fibrosis and myocyte loss, with immunohistochemical analysis showing chronic inflammation consistent with myocarditis. However, the association between oxidative stress/inflammation and genetic DCM in relation to sarcomere protein dysfunction has not been well defined.
Our current studies are also focused on elucidating the effects of glutathionylation on sarcomeric proteins, in particular cardiac myosin binding protein-C, in the clinical context of dysfunction following ischemia- reperfusion injury, using mouse models. Preventing cMyBP-C glutathionylation represents a viable therapeutic approach to improve cardiac function post-ischemia reperfusion injury.
Sakthivel Sadayappan, PhD, MBA
Professor, Department of Internal Medicine
Director of Heart Branch of the Heart, Lung and Vascular Institute
Division of Cardiovascular Health and Disease, College of Medicine
University of Cincinnati
Cardiovascular Center, Rm 4935
231 Albert Sabin Way
Cincinnati, OH 45267-0542, USA
Phone : +1 513-558-7498
Email : email@example.com