Gene offers an athlete's heart without the exercise

June 13, 2013

Researchers at Case Western Reserve University have found that a single gene poses a double threat to disease: Not only does it inhibit the growth and spread of breast tumors, but it also makes hearts healthier.

In 2012, medical school researchers discovered the suppressive effects of the gene HEXIM1 on in mouse models. Now they have demonstrated that it also enhances the number and density of blood vessels in the heart – a sure sign of cardiac fitness.

Scientists re-expressed the HEXIM1 gene in the adult mouse heart and found that the hearts grew heavier and larger without exercise. In addition, the animals' resting heart rates decreased. The lowered heart rate indicates improved efficiency, and is supported by their finding that transgenic hearts are pumping more blood per beat. The team also discovered that untrained ran twice as long as those without any genetic modification.

"Our promising discovery reveals the potential for HEXIM1 to kill two birds with one stone – potentially circumventing heart disease as well as cancer, the country's leading causes of death," said Monica Montano, PhD, associate professor of pharmacology, member of the Case Comprehensive Cancer Center, who created the mice for the heart and and one of the lead researchers.

Hypertension and subsequent are characterized by a mismatch between the heart muscles' need for oxygen and nutrients and blood vessels' inability to deliver either at the rate required. This deficit leads to an enlarged heart that, in turn, often ultimately weakens and stops. The researchers showed that increasing through the artificial enhancement of HEXIM1 levels improved overall function – HEXIM1 may be a possible for heart disease.

The study, published online in the peer-reviewed journal Cardiovascular Research, is the sixth from the team of Dr. Montano and Michiko Watanabe, PhD, professor of pediatrics, genetics, and anatomy at Case Western Reserve School of Medicine and director of Pediatric Cardiology Fellowship Research at Rainbow Babies and Children's Hospital. Their collaboration began in 2004 with an investigation of why mice expressing mutant HEXIM1 suffered heart failure in the fetal stages of life. The research team found then that the gene is important for cardiovascular development and that it is abundant in the earliest months of life. This discovery led the team to explore whether increasing HEXIM1 levels could help reverse cardiovascular disease by encouraging vessel growth.

"Our Cleveland-based collaborative research teams revealed that increasing HEXIM1 levels brought normal functioning hearts up to an athletic level, which could perhaps stand up to the physical insults of various cardiovascular diseases," Watanabe said.

The results build on the team's findings last year that showed increased levels of HEXIM1 suppressed the growth of breast cancer tumors. Using a well-known of breast cancer metastasis, researchers induced the gene's expression by locally delivering a drug, hexamethylene-bisacetamide using an FDA-approved polymer. The strategy increased local HEXIM1 levels and inhibited the spread of breast cancer. The team is currently making a more potent version of the drug and intends to move to clinical trials within a few years.

"Many cancer drugs have detrimental effects on the heart," said Mukesh K. Jain, MD, FAHA, professor of medicine, Ellery Sedgwick Jr. Chair and director of Case Cardiovascular Research Institute at Case Western Reserve School of Medicine. "It would be beneficial to have a cancer therapeutic with no adverse effects on the heart and perhaps even enhance its function."

The Case Western Reserve-led research team is now investigating HEXIM1's ability to improve the health of mice with cardiovascular disease. They are investigating the drug's ability to reduce the damage from attacks.

Explore further: Putting a 'HEX' on muscle regeneration

Related Stories

Putting a 'HEX' on muscle regeneration

October 1, 2012
A complex genetic regulatory network mediates the regeneration of adult skeletal muscles. In this issue of the Journal of Clinical Investigation, researchers at the State University of New York Downstate Medical Center in ...

MRI detects early effects of chemotherapy on children's hearts

June 9, 2013
MRI scans of children who have had chemotherapy can detect early changes in their hearts finds research in biomed Central's open access journal Journal of Cardiovascular Magnetic Resonance.

Lifespan-extending drug given late in life reverses age-related heart disease in mice

June 10, 2013
Elderly mice suffering from age-related heart disease saw a significant improvement in cardiac function after being treated with the FDA-approved drug rapamycin for just three months. The research, led by a team of scientists ...

African-American breast cancer survivors face higher risk of heart failure

March 7, 2013
African-American women who survive breast cancer are more likely to develop heart failure than other women who have beaten the disease, according to research being presented at the American College of Cardiology's 62nd Annual ...

Breastfeeding can reduce maternal breast cancer and heart disease, and save $17 billion in societal costs, study finds

June 7, 2013
(Medical Xpress)—Mothers who breastfeed are at significantly lower risk of developing breast cancer, hypertension and suffering heart attacks than women who do not, according to researchers at Harvard Medical School and ...

Researchers discover new molecule linked to late-stage breast cancer

December 17, 2012
Researchers at Case Western Reserve University School of Medicine have identified a molecule linked to more aggressive forms of breast cancer – a discovery that could point the way to potential cures.

Recommended for you

The 16 genetic markers that can cut a life story short

July 27, 2017
The answer to how long each of us will live is partly encoded in our genome. Researchers have identified 16 genetic markers associated with a decreased lifespan, including 14 new to science. This is the largest set of markers ...

A rogue gene is causing seizures in babies—here's how scientists wants to stop it

July 26, 2017
Two rare diseases caused by a malfunctioning gene that triggers seizures or involuntary movements in children as early as a few days old have left scientists searching for answers and better treatment options.

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.