Cardiovascular disease claims a life every 40 seconds. In the U.S. alone, every year 550,000 people have a heart attack for the first time. Preventing heart failure has been a major challenge in the management of cardiovascular diseases.
Currently, β-adrenergic blockades — or β-blockers — are medications that have been used to treat abnormal heart rhythms to protect from a heart attack after a first heart attack has occurred. While β-blockers have proven effective in treating chronic congestive heart failure, the long-term benefit of decreasing contractile kinetics is not completely understood.
With the help of a $1.58 million grant from the National Heart, Lung and Blood Institute of the National Institutes of Health, a research team from Wayne State University will establish a targeted approach to sustain cardiac function during an energetic crisis and heart failure, and ultimately provide methods for early detection and better monitoring of heart disease.
The study, “Modification of troponin T to improve cardiac function in heart failure,” will use integrative research approaches to establish the underlying mechanism for the physiological modification of cardiac troponin T — proteins in the blood that are released when the heart muscle has been damaged that can differentiate between unstable angina and heart attack — with the ultimate goal of developing a new approach for the treatment of heart failure.
Led by Jian-Ping Jin, M.D., Ph.D., professor and William D. Traitel Endowed Chair of Physiology in the School of Medicine at Wayne State, the research team has focused on the area of protein structure-function relationships, particularly on protein engineering to improve muscle and heart functions.
According to Jin, the restrictive removal of a regulatory segment of cardiac troponin T occurs when the heart is under stress to selectively tune down contractile velocity of cardiac muscle and elongate the ejection time, which increases pumping volume with a minimized energetic cost. Together with its value in diagnostic measurements of cardiac function and adaptation, this novel mechanism provides a promising molecular target to develop new treatment of heart failure.
“The results from this project will establish a targeted approach to sustain cardiac function during energetic crisis and heart failure,” Jin said. “With multilevel and integrative investigations, our study will lay the groundwork for translating this molecular mechanism into a new clinical treatment for heart failure.”
In addition to the primary research award, Jin was also awarded an Administrative Supplement for Participation in the National Institutes of Health’s Concept to Clinic Innovation (C3i) Program. Under the program, Jin will evaluate the clinical and market opportunities of the novel biomarker for the detection of cardiac ischemia prior to death of cardiomyocytes. The biomarker could significantly impact the diagnosis and treatment options for patients presenting with heart failure.
“The C3i program is an excellent opportunity for the investigators to engage with industry mentors to understand the value proposition and commercialization roadmap for their technology, and serves as a catalyst for bringing the technology to the clinic and marketplace,” said Joan Dunbar, associate vice president for technology commercialization at Wayne State. “This is the first Wayne State team to participate in the program, and we are very excited for the opportunity it presents.”
The Wayne State team for the C3i program includes Jin as the scientific and technical lead; Phillip Levy, M.D., MPH, FACEP, FAHA, FACC, the Edward S. Thomas Endowed Professor and associate chair of research – Department of Emergency Medicine and assistant vice president for translational science and clinical research innovation as the clinical advisor; and Jeremiah Shields, a graduate of Wayne State’s Innovation Fellows program, as the business development lead.
The grant number for this National Institutes of Health award is HL-138007.