Help for failing hearts. According to the American Heart Association, nearly five million Americans are living with heart failure, and 550,000 new cases are diagnosed each year. People with heart failure generally have enlarged hearts, a condition called hypertrophy, which results from the enlargement of myocytes — the heart muscle cells that cause the heart to beat.

Research has shown that a group of molecules known as reactive oxygen species (ROS) are involved in the enlargement of the myocytes, but until recently little was known about the specific mechanisms that lead to hypertrophy. An investigation by a group of researchers headed by Wilson Colucci, a MED professor and chairman of cardiovascular medicine and chief of cardiology at Boston Medical Center, recently shed new light on this process, opening the way for the development of new treatments.

The researchers studied heart muscle cells from rats. They knew that stimulating a-adrenergic receptors — a class of molecules that carry information into cells — activates a small protein called Ras, and that Ras in turn stimulates enlargement of myocytes.

The study revealed that when a-adrenergic receptors are stimulated, they produce ROS that change the Ras protein, specifically a portion of the protein known as a thiol (sulfur and hydrogen atoms that are bonded to one or more of the carbon atoms in the protein). This process is called oxidative modification. ROS, or free radicals, are ubiquitous in the body, produced by incomplete cellular processes.

The researchers also found that Ras thiols were protected from oxidative modification by the protein thiroedoxin-1. Further, they found that preventing oxidative modification of the thiols prevented enlargement of the myocytes.

“This is the first direct demonstration of the specific molecule targeted by ROS that leads to enlargement of heart muscle cells,” says Colucci. On the basis of this understanding, the researchers hope that new treatments will be developed to protect thiols and prevent hypertrophy and heart failure.

Their research was reported in the February 22 issue of the journal Circulation.

The silver lining. Women being treated with tamoxifen, a drug commonly used to prevent recurrence of breast cancer, may experience an upside to this painful and devastating disease. Researchers at the Schools of Medicine and Public Health recently completed a study showing that women taking tamoxifen may also be reducing their risk of heart attack.

The team, including Susan Jick, a MED associate professor who works at the Boston Collaborative Drug Surveillance Program, Timothy Lash, an SPH assistant professor of epidemiology, Brian Bradbury, an SPH research associate, and James Kaye, a MED research associate, based their study on data from the General Practice Research Database, one of the world’s largest computerized databases of primary care medical records. It includes information about three million patients collected from almost 400 primary care practices throughout the United Kingdom since 1987.

The researchers reviewed the records of women between the ages of 30 and 85 who had been treated for cancer between January 1991 and December 1999 — 3,030 who were treated with tamoxifen for breast cancer and 4,233 who had other cancers and did not receive tamoxifen.

The analysis revealed that while women were using tamoxifen their risk of a first heart attack or of experiencing angina — chest pain associated with stress on the heart — was significantly reduced. The decreased risk was seen in women who had completed less than two years of tamoxifen therapy and continued during the five years of recommended therapy.

Previous studies had shown that women being treated with tamoxifen had lower levels of other indicators of heart disease, such as LDL cholesterol and homocysteine, an amino acid that in combination with LDL cholesterol builds fatty plaques in the coronary arteries. Tamoxifen has been shown to reduce the risk of breast cancer recurrence by as much as 50 percent, but taking it beyond five years is not generally recommended, as long-term treatment has been associated with an increased incidence of endometriosis.

The study was published in the March 15 issue of the journal Cancer.