Research Identifies Potential Path to Drug Targets to Minimize Heart Attack Muscle Damage

A heart attack due to blockage of a coronary artery causes heart muscle damage that is progressive during the next few hours. The sooner this blockage is relieved, the less the heart muscle is damaged (time is muscle). Unfortunately reperfusion (resuming the blood flow) does not immediately stop the damage. This combination is known as ischemia/ reperfusion injury.

Basic research scientists recently discovered intracellular mechanisms responsible for this ischemia/reperfusion injury, paving the way for drug targets to inhibit and potentially minimize heart damage.

Sarver Heart Center member Henk Granzier, PhD, professor of Physiology and Biomedical Engineering at the UA College of Medicine, collaborated with Richard Schulz, PhD, professor in the Departments of Pediatrics and Pharmacology at the Cardiovascular Research Center at the University of Alberta, Canada, to discover a possible major breakthrough. Their research is reported in the Nov. 2, 2010 issue of Circulation.

Through painstakingly complex basic research studies, the research teams discovered that matrix metalloproteinases (MMPs) localized inside the cardiac muscle cell on a specific region of the largest-known protein (titin) to cause heart-cell damage. On ischemia/reperfusion injury, MMP is activated and breaks down titin, impairing its crucial roles in the muscle function of the heart . Importantly, pharmacologic inhibition of MMP-2 reduces the damage, explains Dr. Granzier, the Allan and Alfie Norville Endowed Chair in Sarver Heart Center’s Molecular Cardiovascular Research Program and a member of the UA’s BIO5 Institute.

Dr. Granzier is a leading investigator in the pathophysiology of titin and was a collaborator and
major contributor to this important basic research discovery.

“From a clinical perspective, this research has the potential to lead to the development of medicines that would be used with clot-busting drugs or cardiac catheterization to minimize heart muscle damage from a heart attack. This is an exciting finding and an excellent example of the University’s emphasis on bench-to-bedside research,” said Gordon A. Ewy, MD, director of the Sarver Heart Center.

Granzier Selected as Co-investigator on International Grant

Dr. Hendrikus L. Granzier, PhD, Awarded $1.5 million Grant to Study Role of Titin in Heart Function and Disease