New molecule promotes cardiovascular protection without cancer risk

Researchers have found a way for women to get the beneficial effects of estrogen without increasing their risk of cancer, according to a study conducted at the University of Texas Southwestern Medical Center.

Philip Shaul, MD, professor of pediatrics, and colleagues created a synthetic molecule, a unique selective estrogen recaptor modulator (SERM), and tested it in mice to determine the biological mechanisms by which estrogen promotes blood vessel health. To mimic diseased arteries in the heart and brain that cause heart attacks and strokes, researchers examined female mice with high cholesterol and injured carotid arteries, which become substantially blocked if the ovaries have been removed.

The team found that when they treated the injured mice with the new molecule, the arteries remained clear and unobstructed.

“We have discovered that the small population of estrogen receptors outside the nucleus of endothelial cells has a unique means to activate cell growth and migration, which are important to blood vessel maintenance and repair, and to regulate the production of nitric oxide, which is a protective molecule in the vascular system,” Dr. Shaul explained. “Whereas all existing estrogen-related drugs change the function of the nuclear receptors which stimulate cancer cell growth, the synthetic molecule targets only the non-nuclear estrogen receptors. We're at the stage where we can start to think about how to translate these findings to humans.”

Researchers also reported that when they studied how normal and cancerous uterine cells responded to the synthetic molecule, estrogen caused robust growth of both normal and cancerous uterine cells while the synthetic molecule did not.

“The findings strongly suggest that the molecule helps maintain vascular health without adverse impact on cancer risk,” Dr. Shaul concluded. “This approach is likely applicable to both men and women and not limited to older individuals.”

The study's findings were published in the Journal of Clinical Investigation. (2010 Jun 23. pii: 38291. doi: 10.1172/JCI38291. [Epub ahead of print]).

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