A Protein Switch May Turn On Heart Cells To Combat Heart Disease

November 08, 1998

DALLAS, Nov. 8 -- Scientists are finding ways to switch on and off key proteins that may make heart cells come out of biological "dormancy" and replace the damaged cells that result from heart disease. Their research was reported today in two presentations at the American Heart Association's 71st Scientific Sessions.

Unlike most other cells in the body, heart muscle cells, called myocytes, are believed to stop multiplying shortly after birth and do not regenerate, even if they are damaged, say the researchers. Because heart muscle cells can not generate new cells, they enlarge to accommodate growth of the heart and to take over the functioning of cells damaged by a heart attack or other conditions, such as high blood pressure, that stress the heart.

"After a heart attack, or in response to stresses on the heart, myocytes will get bigger. However, these bigger heart cells don't work as well," says W. Robb MacLellan, M.D., assistant professor in the Cardiovascular Research Laboratories at the University of California at Los Angeles School of Medicine.

"We're trying to find a way to get the cells to multiply instead of enlarge," he says. Cells that enlarge cause a condition known as left-ventricular hypertrophy, which can increase the risk of developing congestive heart failure.

MacLellan and colleagues say the research may lead to new "gene therapy" to treat heart enlargement and improve heart function in people who have heart disease.

Based on an earlier study suggesting that the "retinoblastoma" gene was critical in controlling cell division, MacLellan and his colleagues focused on the protein that this gene produces retinoblastoma protein, called Rb. Scientists believe the Rb protein may help keep heart cells "dormant" so they no longer can divide. To test this theory, MacLellan's group "turned off" the Rb in a group of mice. Researchers compared heart sizes between the genetically altered mice and mice who still had the Rb gene on in their hearts.

Scientists noticed that the heart cells continued to divide for a longer time in the genetically altered mice (those without the heart Rb gene). At eight weeks of age the hearts in mice without Rb were 8 percent bigger than the hearts of mice that still had the Rb gene active in their heart cells.

While this represents an important step forward in manipulating cells in the heart to grow, MacLellan says researchers still must investigate how the Rb gene works over time and whether these heart cells will multiply after a stress, such as heart attack.

Extending these studies, MacLellan and colleagues identified a protein in the heart that binds to Rb. Called MRP1, this protein appears to oppose Rb's effects in the heart and is turned off by binding to Rb. Although the full effects of this protein are to be determined, it appears that MRP1 can return cells to an earlier phase similar to fetal cells.

While fetal heart cells are capable of dividing, shortly after birth these cells stop dividing and express specialized "adult" genes. "We think Rb and MRP1 are key parts of this process. If we can turn on MRP1 in adult cells, we may be able to get them to 'think' they are fetal cells and start dividing," he says. "Now we are searching for the right combination of these factors to trigger cell division. We hope by overcoming Rb, possibly with MRP1, we can set the heart cells up so that with the right stimulus they will divide," MacLellan says.

They hope that the same signals that stimulate dormant heart cells to enlarge -- such as stress from high blood pressure or having to "take up the slack" for damaged cells after a heart attack -- may be able to stimulate cells treated with MRP1 to divide and replace the damaged cells, he says.

Co-authors are Michael Schneider, M.D.; Marc Voorjuis, Ph.D.; Peter Frenkel, M.D.; and Anton Berns, Ph.D.
-end-
For more information Nov. 8-11
contact Carole Bullock or Brian Henry
Dallas County Convention Center
(214) 853-8056
-end-


American Heart Association

Related Heart Disease Articles from Brightsurf:

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

New 'atlas' of human heart cells first step toward precision treatments for heart disease
Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in research published in the journal Nature.

With a heavy heart: How men and women develop heart disease differently
A new study by researchers from McGill University has uncovered that minerals causing aortic heart valve blockage in men and women are different, a discovery that could change how heart disease is diagnosed and treated.

Heart-healthy diets are naturally low in dietary cholesterol and can help to reduce the risk of heart disease and stroke
Eating a heart-healthy dietary pattern rich in vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils and nuts, which is also limits salt, red and processed meats, refined-carbohydrates and added sugars, is relatively low in dietary cholesterol and supports healthy levels of artery-clogging LDL cholesterol.

Pacemakers can improve heart function in patients with chemotherapy-induced heart disease
Research has shown that treating chemotherapy-induced cardiomyopathy with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.

New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.

Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.

Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.

Read More: Heart Disease News and Heart Disease 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.