New information about heart enzymes could lead to better treatments

April 02, 2004

WINSTON-SALEM, N.C. - New evidence in animals about hormones that regulate blood pressure and heart function could lead to better treatments for humans after heart attacks, say researchers from Wake Forest University Baptist Medical Center.

"We've learned more about the complex system of enzymes and hormones that regulates the cardiovascular system," Carlos Ferrario, M.D., director of the Hypertension and Vascular Disease Center and lead author of the study, reported in the on-line edition of Hypertension. "We believe this new knowledge could lead to more effective drugs with fewer side effects."

In rats, the researchers found that the drugs olmesartan and losartan helped reverse changes in the heart that can lead to heart failure, a condition in which the heart doesn't pump enough blood to meet the body's needs. These two drugs have fewer side effects than the standard therapy currently given to humans.

After a heart attack, the damaged area of heart muscle often becomes thin and the remainder of the heart muscle becomes thick and flabby. These changes, which are known as remodeling, can lead to heart failure.

To prevent remodeling, patients are currently given drugs called ACE (angiotensin converting enzyme) inhibitors that prevent the formation of angiotensin II, a hormone that promotes remodeling. By studying rats after heart attacks, the investigators learned more about angiotensin II - information that may be used to develop more targeted medications.

The investigators studied rats with normal blood pressure. Three groups of rats had surgery to simulate a heart attack. These animals were then given either losartan, olmesartan or an inactive saline solution for 28 days. A fourth group of animals got a sham operation and no treatment.

While ACE inhibitors block the production of angiontensin II, losartan and olmesartan are both designed to block its function and have fewer side effects. Researchers found that losartan and olmesartan were both effective in the rats at reversing changes that cause remodeling.

The researchers also found that rats in the active treatment groups had increased levels of ACE2 and angiotensin 1-7, which both benefit heart function

ACE2 was discovered in the hearts of mice in 2002 by Wake Forest Baptist researchers and colleagues at other research centers. Mice that were bred without the enzyme had infrequent heart beats by middle age, leading researchers to believe it played an important role in heart function. ACE2 has since been identified in the human heart.

Angiotensin 1-7, a hormone that can dilate blood vessels, prevent remodeling and oppose the action of angiotensin II, was discovered by Ferrario and colleagues about 12 years ago.

"We believe that ACE2 may be a natural mechanism for protecting the heart," said Ferrario. "It seems to limit levels of angiotensin II by degrading it into angiotensisn 1-7. This research was the first demonstration to show that by blocking the receptor for angiotensin II, we can stimulate the production of ACE2."

Ferrario said the finding could one day lead to new therapies that will be based on the increasing the levels of angiotensin 1-7 by targeting the production of ACE2.
-end-
Media Contacts: Karen Richardson, (krchrdsn@wfubmc.edu) or Shannon Koontz (skoontz@wfubmc.edu) 336-716-4587.

About Wake Forest University Baptist Medical Center: Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University School of Medicine. It is licensed to operate 1,282 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.

Wake Forest Baptist Medical Center

Related Heart Attack Articles from Brightsurf:

Top Science Tip Sheet on heart failure, heart muscle cells, heart attack and atrial fibrillation results
Newly discovered pathway may have potential for treating heart failure - New research model helps predict heart muscle cells' impact on heart function after injury - New mass spectrometry approach generates libraries of glycans in human heart tissue - Understanding heart damage after heart attack and treatment may provide clues for prevention - Understanding atrial fibrillation's effects on heart cells may help find treatments - New research may lead to therapy for heart failure caused by ICI cancer medication

Molecular imaging identifies link between heart and kidney inflammation after heart attack
Whole body positron emission tomography (PET) has, for the first time, illustrated the existence of inter-organ communication between the heart and kidneys via the immune system following acute myocardial infarction.

Muscle protein abundant in the heart plays key role in blood clotting during heart attack
A prevalent heart protein known as cardiac myosin, which is released into the body when a person suffers a heart attack, can cause blood to thicken or clot--worsening damage to heart tissue, a new study shows.

New target identified for repairing the heart after heart attack
An immune cell is shown for the first time to be involved in creating the scar that repairs the heart after damage.

Heart cells respond to heart attack and increase the chance of survival
The heart of humans and mice does not completely recover after a heart attack.

A simple method to improve heart-attack repair using stem cell-derived heart muscle cells
The heart cannot regenerate muscle after a heart attack, and this can lead to lethal heart failure.

Mount Sinai discovers placental stem cells that can regenerate heart after heart attack
Study identifies new stem cell type that can significantly improve cardiac function.

Fixing a broken heart: Exploring new ways to heal damage after a heart attack
The days immediately following a heart attack are critical for survivors' longevity and long-term healing of tissue.

Heart patch could limit muscle damage in heart attack aftermath
Guided by computer simulations, an international team of researchers has developed an adhesive patch that can provide support for damaged heart tissue, potentially reducing the stretching of heart muscle that's common after a heart attack.

How the heart sends an SOS signal to bone marrow cells after a heart attack
Exosomes are key to the SOS signal that the heart muscle sends out after a heart attack.

Read More: Heart Attack News and Heart Attack Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.