When a good molecule goes wrong. new research suggests that chemical changes in HDL help clear cholesterol deposits, contributing to clogged arteries.
PHILADELPHIA - Despite the name, not all "good" cholesterol can be good for everyone. In patients whose coronary arteries are clogged with plaques, up to half of the high-density lipoprotein (HDL), the particle that carries the good cholesterol, is chemically modified so that it can fight against the accumulation of cholesterol deposits, researchers reported here on August 25 at a meeting of the American Chemical Society. The new work should lead to improved diagnosis of heart disease, as well as new drugs that prevent atherosclerosis by blocking the damage to HDL.
The research is an offshoot of efforts to find better ways to track heart disease risk. Last year, Stanley Hazen, a physician and chemist at the Cleveland Clinic in Ohio and colleagues identified two chemical fingerprints that were much better than existing markers to highlight the risk of heart disease a person . The first of these markers was myeloperoxidase (MPO), a key enzyme that immune cells use to fight microbial invaders. Of the patients who need emergency care for chest pain, those with high levels of MPO had a higher short-term risk of heart attacks, bypass surgery, or death. The second was a set of proteins modified by the addition of a chemical group known as nitrotyrosine, a reaction which can be carried by MPO and other compounds. Patients with high levels of nitrotyrosine these modified proteins were more likely to have atherosclerosis. Hazen's group wanted to know if a particular protein is more likely than others to be hit with nitrotyrosine.
They found that the preferred target of DFO is apolipoprotein A-1 (ApoA-1), the primary HDL protein. And when they looked at blood samples from 0 patients, half with and half without cardiovascular disease, they found that patients with lots of apoA-1 were changed 16 times more likely to belong to the group with heart disease . However, currently used clinical markers - cholesterol and C-reactive protein - are far worse to predict disease. The results also appear in the current Journal of Clinical Investigation . Hazen suggests that when DFO reacts with apoA-1, it changes the protein to one or more key sites interfere with the ability of the protein to transport cholesterol out of cells and eventually leading to atherosclerosis.
"This is very exciting," said Ian Blair, a disease biomarker expert at the University of Pennsylvania in Philadelphia. "He seems to have a biomarker that is much better than existing biomarkers for diseases cardiovascular. "Moreover, he adds, for the first time the new work provides a clear molecular mechanism that explains why high HDL levels may not always have a protective effect against heart disease. Hazen said his group and others are already working on the follow-MPO diagnostic, and pharmaceutical companies are looking for compounds to inhibit MPO and prevent HDL deactivation.
Related Sites
Stanley Hazen's website
atherosclerosis bases of the American Heart Association
cholesterol bases of the American Heart Association
0 Komentar