Anastasios Lymperopoulos, Ph.D., assistant professor of pharmacy, discovered that a protein contributes to heart failure. He started the research at Thomas Jefferson University in early 2008 and completed it at NSU.
Lymperopoulos’s colleague Luigi Cubeddu, M.D., Ph.D., professor of pharmaceutical sciences, said that heart failure is a disabling condition in which the heart loses the ability to generate good cardiac output. He said that Lymperopoulos’s discovery is significant.
“Dr. Lymperopoulos is working on understanding the mechanism by which heart attacks damage the cardiac muscle, which leads to heart failure, so that is of extreme clinical significance worldwide,” Cubeddu said. “Around 50 million Americans have heart failure, and heart failure comes most commonly from cor-onary artery disease, and anything we can do to prevent coronary artery disease and heart failure is good.”
Lymperopoulos discovered that a protein called beta-arrestin 1, which regulates several receptors important to cardiac function, increases the levels of aldosterone, a hormone that negatively affects the heart.
Lymperopoulos said that aldosterone is produced by the adrenal gland and normally has useful effects on the body such as limiting the amount of sodium and water lost in urination. For example, when someone is dehydrated, the body produces aldosterone to maintain the proper volume of blood, water and tissue fluid.
However, when the heart is failing, aldosterone is produced in excessive amounts and has toxic effects on the heart. Heart failure is usually caused by a heart attack or another injury that destroys the heart’s tissue. As a result, the heart has fewer cells to pump blood and starts failing. Lymperopoulos said that through a variety of direct effects on the heart, aldosterone makes the heart build other tissues like collagen to replace the lost heart tissue.
“It’s basically scar tissue that replaces the lost functional tissue of the heart,” he said. “But, of course, you don’t want that in heart failure because this tissue is useless for the heart.”
Lymperopoulos said that aldo-sterone is produced in excessive amounts in heart failure because of angiotensin II, another hormone that increases blood pressure. He said he found that angiotensin II produces aldosterone through beta-arrestin 1, a protein from the adrenal gland.
“Our protein, beta-arrestin 1, does not cause heart failure. It merely makes it worse. We’re not claiming that by inhibiting it we will cure heart failure,” Lymperopoulos said. “We’ll just help patients do better and improve their symptoms. Beta-arrestin 1 jumps in after heart failure has been established and it promotes aldosterone, putting more burden on the heart, which is already failing.”
Lymperopoulos said that inhibiting this protein either by gene therapy, inserting genes to express inhibitors of this protein in patients, or by the development of new drugs will help heal heart failure.
Lymperopoulos said that besides the death of heart tissue, other factors that can cause heart failure include genetic defects, high blood pressure, diet and atherosclerosis, which is the hardening and gradual blockage of the arteries, and certain drugs such as Doxorubensen, an oncology drug, which is known to be cardiotoxic. Heart failure can also be caused by excessive levels of adrenaline.
“Chronic stress elevates adrenaline and that’s why chronic stress is bad for your heart because it will eventually cause heart failure,” Lymperopoulos said.
Lymperopoulos said he hopes pharmaceutical companies that work on the inhibitors of beta-arrestin 1’s pathway will pick up on his discovery and use it to develop new drugs. He also said he hopes cardiologists will see his discovery.
“I really hope it catches the eye of clinical cardiologists and brings better focus on this protein in cardiovascular disease and particularly heart failure,” he said.
Lymperopoulos is testing the ability of Cozaar, Atacand and Diovan, drugs used for heart conditions, to inhibit beta-arrestin 1 and the impact of their degree of inhibition on cardiac function.
“All these drugs are not equal when it comes to their effects on the heart,” he said. “If they have differences in their ability to inhibit this protein, that might explain differences in their effectiveness in treating heart failure.”
The Journal of the American College of Cardiology will publish Lymperopoulos’s discovery in its January 2011 issue. He said he has big hopes for another project that he is looking to develop and set up with Jackson Memorial and University of Miami to study the role of beta-arrestin 1 in adrenal endocrinological disorders like Cushing’s syndrome.
