A study by University of Hawaiʻi researchers identifies a molecular pathway that may help reduce the damaging effects of an enlarged heart caused by hypertension or a heart attack.
The study by researchers in UH Hilo’s College of Pharmacy and UH Mānoa’s John A. Burns School of Medicine demonstrates for the first time that stretching of cardiac cells in cardiac hypertrophy promotes secretion of a protein that helps protect cardiac function and keep cardiac cells alive.
Study co-authors are Eugene Konorev of the UH Hilo College of Pharmacy, and Michelle Matter, Anna Leychenko and Mayumi Jijiwa of the UH Mānoa Department of Cell and Molecular Biology.
Konorev says the value of the study is in delineating of intracellular events in stretched cardiac myocytes that lead to the increased expression of Vascular Endothelial Growth Factor or VEGF.
“Release of vascular endothelial growth factor by the growing myocardium ensures the concomitant growth of cardiac vascular networks, or angiogenesis,” says Konorev. “Enhanced blood supply resulting from angiogenesis supports the normal function of the growing heart.”
Normally, VEGF creates new blood vessels during embryonic development and promotes vessel development following injury or lack of oxygen. In a study using rats, the researchers found that when enlargement of the heart stretches cardiac cells, they release VEGF.
“We have found that stretch of adult cardiac cells promotes release of VEGF through activation of the NFkB signaling pathway,” Matter says. Blocking NFkB activation abrogates VEGF secretion induced by cyclic mechanical stretch in these cells.
“Targeting this molecular pathway may alleviate the pathological effects of hypertrophy and increase survival of patients who have had a heart attack or suffer hypertension,” Matter says.
Heart disease in Hawaiʻi
More than 3,100 people in Hawaiʻi die of cardiovascular disease each year, according to The Burden of Heart Disease in Hawaiʻi, a report to the state Department of Health.
As many as 70 percent of the adults in Hawaiʻi have at least one risk factor for cardiovascular disease, including diabetes, hypertension and obesity, and Big Island residents, Native Hawaiians, Filipinos and the poor have higher risks for cardiovascular disease, according the DOH report.
About the study
Eugene A. Konorev is an assistant professor in the Department of Pharmaceutical Sciences of UH Hilo’s College of Pharmacy. He studies mechanisms of apoptosis in cardiomyocytes and endothelial cells as underlying factors in the development of cardiomyopathies and heart failure. He has been studying mechanisms of ischemia-induced cardiac injury and cardiovascular complications of anti-cancer therapy using cellular and animal models.
Konorev’s lab at UH Hilo is currently studying the mechanisms of new vessel formation, or angiogenesis, in the settings of cardiac diseases and tumor growth, with the goals of optimizing anticancer therapy, inhibiting tumor growth, and preventing/delaying the development of cardiac disease conditions. His lab seeks to identify novel natural and synthetic compounds that will modulate the formation of new vascular networks.
Konorev received his doctor of philosophy in pharmacology and doctor of medicine at Kursk Medical University, Russia.