According to the American Heart Association, nearly 5 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. It results from the enlargement of individual heart muscle cells, or myocytes – the cells that actually cause the heart to beat.

Researchers know 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, chairman of the department of cardiology at the School of 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 for this all too common disease.

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

The study revealed that when α-adrenergic receptors are stimulated they produce ROS that 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 known as oxidative modification. ROS are ubiquitous in the body, produced by incomplete cellular processes. They are also known as free radicals.

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

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

This research was reported in the journal Circulation (E-published ahead of print February 22, 2005)

— Joan Schwartz

Image: Effects of TRX1 overexpression on alphaAR-stimulated hpertrophy in adult rat cardiac myocytes.