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Heart Disease: Iron in the Arteries
By Adam Marcus

Too much iron in the blood has been blamed for heart disease, but proving the case against the mineral has been difficult. Now, using the new tools of proteomics, scientists have found that patients with clogged coronary arteries have elevated levels of a key iron-storage protein in their blood vessels.

The protein, called ferritin light chain, is about twice as prevalent in the arteries of sick people as it is in those without blood vessel disease.

Chemical structure of ferritin with red blood cells.

The discovery supports the 'iron hypothesis' of the risk for heart disease, says Qing Wang, a molecular geneticist at the Cleveland Clinic and a co-author of the study.

The iron hypothesis, proposed in 1981, says that men and post-menopausal women are at higher risk for coronary artery disease than pre-menopausal women because these two groups have higher amounts of iron stored in their bodies.

“When ferritin light chain expression is increased in the coronary arteries, there will be more iron stored there,” Wang says. “We think that too much iron will probably lead to too many oxygen free radicals, and that may damage the coronary arteries.”

Wang's group looked for differences in protein activity in ten people with coronary artery disease and seven with healthy blood vessels. They measured the size and electric charges and of all the proteins in vessel cells.

“We clearly see the difference between the normal group” and the group with diseased coronary arteries, says Wang, whose study appeared in Physiological Genomics.

Although the study implicates ferritin light chain in coronary artery disease, it's not yet clear that elevated levels of the protein cause vessel problems or simply reflect them. The protein may prove to be a useful biochemical marker for the disease.

“We cannot exclude yet the possibility that this is a consequence of the disease process,” notes Wang.

The new research is among the first applications of proteomics to the origins of coronary artery disease, but it won't be the last.

"Protein is where the action is," says cardiologist Victor Dzau, chairman of the Department of Medicine at Brigham and Women’s Hospital in Boston, and editor of Physiological Genomics. Although the latest findings must be replicated, Dzau calls it a “litmus test” for the utility of proteomics in the study of heart ailments.

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You, SA. et al. Proteomic approach to coronary atherosclerosis shows ferritin light chain as a significant marker: evidence consistent with iron hypothesis in atherosclerosis. Physiol Genomics 13, 25-30 (March 18, 2003).

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