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Study explains how heart attack can lead to heart rupture
Date:11/17/2011

ent in the UI Medical Scientist Training Program; Mei-Ling Joiner, Ph.D.; Madhu Singh, Ph.D.; Elizabeth Luczak, Ph.D.; and Paari Swaminathan, M.D., devised a series of experiments in mice to investigate how elevated levels of aldosterone damage heart muscle after a heart attack and how Cam kinase is involved.

The experiments confirmed that aldosterone increases the amount of oxidized, and therefore, activated CaM kinase in heart muscle. Mice given excess aldosterone, mimicking levels seen in human patients, were twice as likely to die after a heart attack as mice that were not given extra aldosterone (70 percent vs. 35 percent), and the cause of death was heart rupture.

Importantly, any treatment that reduced the amount of oxidized CaM kinase or otherwise inhibited CaM kinase activity lowered the risk of cardiac rupture and death in the mice.

Interestingly, the researchers found that activated CaM kinase prompted heart muscle cells to produce an enzyme called MMP9 that is implicated in heart rupture.

"Although there are many sources of this enzyme, our study showed that heart muscle itself is actually making this protein too and is acting against its own self-interest in doing so," Anderson says. "We don't know why it happens, but inhibiting CaM kinase can prevent it."

The MMP9 enzyme is involved in remodeling the "matrix" that surrounds heart cells. This matrix, which acts like mortar between cells, is constantly being broken down and rebuilt. In hearts that rupture after heart attack this remodeling process becomes excessive, weakening the matrix to the point that it ruptures.

Because matrix remodeling plays a role in other diseases, including cancer, Anderson notes that the CaM kinase findings may have clinical implications beyond heart disease.

Overall, the UI study suggests that blocking the biochemical processes triggered by aldosterone might help prevent cardiac rupture following a heart attack.<
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Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-356-7124
University of Iowa Health Care
Source:Eurekalert

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