Nav: Home

Boosting your own defenses against heart disease

March 06, 2017

A protein found in the heart that is known to be involved in cellular stress responses in cancer cells is now believed to play a critical role in the ability of cardiac cells to combat heart disease and recover from a heart attack. A new study led by San Diego State University molecular cardiologist Christopher Glembotski, director of the SDSU Heart Institute, found that the protein appears to promote the natural ability of heart cells to ward off stress-induced damage. This finding suggests a novel treatment and prevention strategy for people at risk of heart disease, according to Glembotski's research.

The protein, known as ATF6, occurs naturally in all cells in the human body. Research by Glembotski's group and others over the years has shown that ATF6 responds to stress brought on by misfolded proteins in a part of the cell called the endoplasmic reticulum. This stress is often caused by an overabundance of reactive oxygen molecules that derail the cell's normal ability to function--the primary reason for damage to the heart when people suffer from heart disease and heart attacks. In previous studies, Glembotski and his colleagues showed that during heart attacks in mice, ATF6 is called into action, but its function in the heart was not known.

To investigate this mystery, Glembotski and his colleagues turned to a strain of mice that lack the gene that codes for the production of ATF6. In these mice, they found that heart disease caused more extensive damage than mice with normally functioning versions of the gene.

Looking further into what other effects the ATF6 protein had in cells, the researchers discovered that it activated a cascade of stress-response genes not previously known to be associated with ATF6. These genes produced an enzyme known as catalase, which acts as an antioxidant and neutralizes harmful reactive oxygen molecules, reducing cellular stress and preventing proteins from misfolding in the first place. By artificially introducing catalase into mice that lacked the ATF6 gene, Glembotski and his team found that these treated mice showed the same protective effects as mice with a working version of the ATF6 gene.

The team went on to show that as mice age, they progressively lose ATF6, and their hearts become more prone to damage during a heart attack. In an effort to arrest this age-related effect, Glembotski and his team developed a drug based on gene therapy that could boost ATF6 production in heart cells. It worked, and the older mice who received the drug showed less damage following a heart attack.

"These cellular mechanics should work very much the same way in humans," Glembotski said. Taken together, the results suggest that ATF6 plays a critical role in jumpstarting a process that reduces ischemia/reperfusion damage (I/R). I/R occurs when blood rushes back into tissue after a heart attack. The researchers reported their findings in the March 3 edition of the journal Circulation Research.

"It seems to be an adaptive response of the heart that is lost with age," Glembotski said. "We think that, like the mice, human heart cells usually make some ATF6, but if they could make more--like in the young heart--the heart would be more resistant to heart disease."

To that end, he and his lab--which has been funded continuously by the National Institutes of Health since 1983--are looking at various ways to boost ATF6 production in the heart. One simple way to do so may be increased exercising.

"Our preliminary studies show that exercise might naturally boost endogenous ATF6 and help prevent damage from I/R," Glembotski said.

An additional way of increasing ATF6 in the heart might involve using a gene therapy to boost naturally occurring ATF6. This could be especially effective for older people whose natural protection against cellular stress has waned.

"As we age, the adaptive stress response in the heart decreases," Glembotski said. "If we can deliver new versions of these genes to the heart, we could bring back some of that protection that you naturally have when you are young."

San Diego State University

Related Heart Disease Articles:

Where you live could determine risk of heart attack, stroke or dying of heart disease
People living in parts of Ontario with better access to preventive health care had lower rates of cardiac events compared to residents of regions with less access, found a new study published in CMAJ (Canadian Medical Association Journal).
Older adults with heart disease can become more independent and heart healthy with physical activity
Improving physical function among older adults with heart disease helps heart health and even the oldest have a better quality of life and greater independence.
Dietary factors associated with substantial proportion of deaths from heart disease, stroke, and disease
Nearly half of all deaths due to heart disease, stroke, and type 2 diabetes in the US in 2012 were associated with suboptimal consumption of certain dietary factors, according to a study appearing in the March 7 issue of JAMA.
Certain heart fat associated with higher risk of heart disease in postmenopausal women
For the first time, researchers have pinpointed a type of heart fat, linked it to a risk factor for heart disease and shown that menopausal status and estrogen levels are critical modifying factors of its associated risk in women.
Maternal chronic disease linked to higher rates of congenital heart disease in babies
Pregnant women with congenital heart defects or type 2 diabetes have a higher risk of giving birth to babies with severe congenital heart disease and should be monitored closely in the prenatal period, according to a study published in CMAJ.
Novel heart valve replacement offers hope for thousands with rheumatic heart disease
A novel heart valve replacement method is revealed today that offers hope for the thousands of patients with rheumatic heart disease who need the procedure each year.
Younger heart attack survivors may face premature heart disease death
For patients age 50 and younger, the risk of premature death after a heart attack has dropped significantly, but their risk is still almost twice as high when compared to the general population, largely due to heart disease and other smoking-related diseases The risk of heart attack can be greatly reduced by quitting smoking, exercising and following a healthy diet.
Citrus fruits could help prevent obesity-related heart disease, liver disease, diabetes
Oranges and other citrus fruits are good for you -- they contain plenty of vitamins and substances, such as antioxidants, that can help keep you healthy.
Gallstone disease may increase heart disease risk
A history of gallstone disease was linked to a 23 percent increased risk of developing coronary heart disease.
Americans are getting heart-healthier: Coronary heart disease decreasing in the US
Coronary heart disease is one of the leading causes of death in the United States.

Related Heart Disease Reading:

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Do animals grieve? Do they have language or consciousness? For a long time, scientists resisted the urge to look for human qualities in animals. This hour, TED speakers explore how that is changing. Guests include biological anthropologist Barbara King, dolphin researcher Denise Herzing, primatologist Frans de Waal, and ecologist Carl Safina.
Now Playing: Science for the People

#SB2 2019 Science Birthday Minisode: Mary Golda Ross
Our second annual Science Birthday is here, and this year we celebrate the wonderful Mary Golda Ross, born 9 August 1908. She died in 2008 at age 99, but left a lasting mark on the science of rocketry and space exploration as an early woman in engineering, and one of the first Native Americans in engineering. Join Rachelle and Bethany for this very special birthday minisode celebrating Mary and her achievements. Thanks to our Patreons who make this show possible! Read more about Mary G. Ross: Interview with Mary Ross on Lash Publications International, by Laurel Sheppard Meet Mary Golda...