For people who initially survive a heart attack, a significant cause of death in the next few days is cardiac rupture -- literally, bursting of the heart wall.
A new study by University of Iowa researchers pinpoints a single protein as the key player in the biochemical cascade that leads to cardiac rupture. The findings, published Nov. 13 as an Advance Online Publication (AOP) of the journal Nature Medicine, suggest that blocking the action of this protein, known as CaM kinase, may help prevent cardiac rupture and reduce the risk of death.
After a heart attack, the body produces a range of chemicals that trigger biological processes involved in healing and repair. Unfortunately, many of these chemical signals can become "too much of a good thing" and end up causing further damage often leading to heart failure and sudden death.
"Two of the medicines that are most effective for heart failure are beta-blockers, which block the action of adrenaline, and drugs that block the angiotensin receptor," explains Mark E. Anderson, M.D., Ph.D., UI professor and head of internal medicine and senior study author. "The third tier of therapy is medication that blocks the action of aldosterone."
Aldosterone levels increase in patients following a heart attack, and higher levels of the hormone are clearly associated with greater risk of death in the days immediately following a heart attack.
Increased aldosterone levels also are associated with a burst of oxidation in heart muscle, and in 2008, Anderson's team showed that oxidation activates CaM kinase. Anderson's research has also shown that CaM kinase is a lynchpin in the beta-blocker and angiotensin pathways.
"We wondered if aldosterone might somehow work through CaM kinase and, if it did, could some of the benefits of aldosterone blockers be attributed to effects on CaM kinase?" Anderson says.
Anderson's team, including co-first authors Julie He, a stud
|Contact: Jennifer Brown|
University of Iowa Health Care