breast cancer

Gene makes heart stronger without exercise

CASE WESTERN RESERVE (US) — A single gene that suppresses breast cancer also makes hearts healthier, a new study shows.

Researchers discovered the suppressive effects of the gene HEXIM1 on breast cancer in mouse models in 2012. Now they have demonstrated that it also enhances the number and density of blood vessels in the heart—a sure sign of cardiac fitness.

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

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“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,” says Monica Montano, associate professor of pharmacology at Case Western University.

Hypertension and subsequent heart failure are characterized by a mismatch between the heart muscle’s 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. Because increasing blood vessel growth through the artificial enhancement of HEXIM1 levels improves overall function, the gene may be a possible therapeutic target for heart disease.

The study, published online in Cardiovascular Research, is the sixth from Montano and colleagues that 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,” says Michiko Watanabe, professor of pediatrics, genetics, and anatomy.

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 mouse model 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,” says Mukesh K. Jain, professor 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 research team is now investigating HEXIM1’s ability to improve the health of mice with cardiovascular disease and the  drug’s ability to reduce the damage from heart attacks.

Case Western Reserve University, the American Heart Association, and the National Institutes of Health supported the research.

Source: Case Western Reserve University

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