Inhibiting CaMKII enzyme activity could lead to new therapies for heart disease

October 11, 2012

University of Iowa researchers have previously shown that an enzyme called CaM kinase II plays a pivotal role in the death of heart cells following a heart attack or other conditions that damage or stress heart muscle. Loss of beating heart cells is generally permanent and leads to heart failure, a serious, debilitating condition that affects 5.8 million people in the United States.

Now the UI team, led by Mark Anderson, M.D., Ph.D., professor and head of internal medicine at the UI Carver College of Medicine, has honed in on how CaM kinase II triggers heart cell death following , showing that the action takes place in the cells' energy-producing mitochondria. In animal tests, the team reports that blocking the enzyme can prevent heart cells from dying, and protects the animals from heart failure.

Mitochondrial are the cells' batteries, generating the energy cells need to work. In , energy produced by these small fuels each heartbeat. However, when the heart is stressed, for example during a heart attack, the mitochondria become leaky and non-functional, which triggers cell death and .

"We found that activity of the CaM kinase II enzyme in mitochondria promotes cell death when the heart is stressed," says Mei-ling Joiner, Ph.D., UI assistant professor of internal medicine and lead author of the study, which was published online Oct. 10 in the journal Nature. "The findings might help us advance treatment of heart diseases and reduce mortality after a heart attack."

The new study shows that activated CaM kinase II promotes leakiness of mitochondria and increases by allowing too much calcium to enter mitochondria. Specifically, the UI team found that CaM kinase II regulates calcium entry into mitochondria by modifying a special mitochondrial . Too much enzyme activity increased the amount of calcium flowing into mitochondria, and this calcium overload triggers cell death.

Using genetically modified mice, the team also showed that inhibiting CaM kinase II activity in mitochondria prevented the calcium overloading, reduced mitochondrial disruption, and protected the mice from heart cell death during heart attack.

These findings provide insight into molecular mechanisms for mitochondrial function and suggest that inhibiting the CaM kinase II enzyme in mitochondria could lead to new and more effective therapies for common forms of .

"Because mitochondria also play important roles in other diseases in brain and skeletal muscle, for example, our findings could also have broad implications for understanding and treating non-cardiac diseases," says Anderson, who also is director of the UI Cardiovascular Research Center.

Explore further: Study explains how heart attack can lead to heart rupture

Related Stories

Study explains how heart attack can lead to heart rupture

November 17, 2011
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.

DNA from heart's own cells plays role in heart failure by mistakenly activating immune system

April 25, 2012
DNA from the heart's own cells plays a role in heart failure by mistakenly activating the body's immune system, according to a study by British and Japanese researchers, co-funded by the British Heart Foundation (BHF). Scientists ...

Recommended for you

Could aggressive blood pressure treatments lead to kidney damage?

July 18, 2017
Aggressive combination treatments for high blood pressure that are intended to protect the kidneys may actually be damaging the organs, new research from the University of Virginia School of Medicine suggests.

Quantifying effectiveness of treatment for irregular heartbeat

July 17, 2017
In a small proof-of-concept study, researchers at Johns Hopkins report a complex mathematical method to measure electrical communications within the heart can successfully predict the effectiveness of catheter ablation, the ...

Concerns over side effects of statins stopping stroke survivors taking medication

July 17, 2017
Negative media coverage of the side effects associated with taking statins, and patients' own experiences of taking the drugs, are among the reasons cited by stroke survivors and their carers for stopping taking potentially ...

Study discovers anticoagulant drugs are being prescribed against safety advice

July 17, 2017
A study by researchers at the University of Birmingham has shown that GPs are prescribing anticoagulants to patients with an irregular heartbeat against official safety advice.

Protein may protect against heart attack

July 14, 2017
DDK3 could be used as a new therapy to stop the build-up of fatty material inside the arteries

Heart study finds faulty link between biomarkers and clinical outcomes

July 14, 2017
Surrogate endpoints (biomarkers), which are routinely used in clinical research to test new drugs, should not be trusted as the ultimate measure to approve new health interventions in cardiovascular medicine, according to ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.