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Unlocking The Secrets Of Heart Failure

March 27, 2002

Unlocking The Secrets Of Heart Failure
2002/03/27

Doctors At The Houston VA Medical Center Examine TNF: The Good And Bad Of An Ancient Protein

HOUSTON, TX - Understanding the good and bad of a 600 million-year-old protein, tumor necrosis factor, may lead to improved strategies for treating heart failure.

"The fact that TNF is produced in the heart and has been around so long suggests that it is there for a reason," said Dr. Douglas Mann, staff physician at the Houston Veterans Affairs Medical Center (HVAMC) and professor of medicine at Baylor College of Medicine.

Getting at the cellular and molecular intricacies of TNF is the mission of Mann's HVAMC research efforts. The lab's research is divided between studying TNF's good and bad effects.

On the good side, Mann's lab proved that TNF protects myocytes, the cells in the heart that contract and enable the heart to pump. Efforts are now underway to determine the molecular mechanisms for this protection.

Understanding the harmful side of TNF also holds promise for heart failure treatments.

"Increased TNF levels have three major effects -- problems with heart contraction, heart dilation, and increased cell death," Mann said. "If we can find ways to control TNF levels, there might be a way to impact the natural history of heart failure."

Heart dilation typically involves an increase in size and thinning of the heart walls. To better understand TNF's association with heart dilation, HVAMC researchers developed two strains of mice.

"One line secretes TNF and the other line, called membrane-bound TNF, secretes TNF but can't release it into the environment," Mann said. "Both provide us with excellent models of different types of heart failure."

The TNF secreting mice develop enlarged hearts with thin walls. These symptoms are models of systolic heart failure, where the heart does not contract well. The membrane-bound TNF mice, models of diastolic heart failure, have hearts with thick, stiff walls that do not relax well.

Both strains of mice provide an opportunity to better understand the processes related to heart failure.

In collaboration with Dr. Blase Carabello, chief of medicine at the HVAMC, the team is looking at the heart mechanics of the two different mouse lines. Gene array analysis also allows the researchers to study the different genes expressed in these two types of heart failure.

"We also can test novel drugs on these mice," Mann said. "Testing new compounds in mice will one day lead to more effective drugs for humans."

Heart failure is a growing epidemic in the United States with 450,000 new cases a year. While five million Americans are affected by the disease today, that number is expected to double in the next 10 years.

"Although we have effective medications, these medications prolong life but don't cure the disease." Mann said. "Clearly there is room for improvement in existing strategies to treat heart failure."

Point of Contact: VHAHOU Public Affairs

04/21/04 08:25