For the first time, scientists have discovered how C-reactive protein, or CRP, is able to access endothelial cells. The UC Davis researchers' findings will be published in the July issue of Arteriosclerosis, Thrombosis, and Vascular Biology, one of the American Heart Association's leading journals.
CRP is a known risk marker for heart disease and, in a study published earlier this year, UC Davis researchers Ishwarlal Jialal and Sridevi Devaraj found that endothelial cells also produce CRP, which is increased 100-fold when cytokines are secreted by human macrophages, a key finding that helps to explain how plaque formation is initiated.
Devaraj and Jialal have now discovered how CRP affects endothelial cells, cells that line the cerebral and coronary arteries, and promotes plaque rupture, leading to heart attacks and strokes. CRP appears to bind to a family of immunoglobulin-processing receptors known as Fc-gamma receptors.
"In this study we convincingly show that CRP binds to two members of the Fc-gamma receptor family, CD64 and CD32, and that by blocking these receptors with specific antibodies, we can reverse the detrimental effects of CRP on endothelial cells," said Jialal, the Robert E. Stowell Chair of Experimental Pathology and director of the Laboratory of Atherosclerosis and Metabolic Research at UC Davis Medical Center.
"This is the first time that anyone has shown how CRP is able to get into the human aortic endothelial cells. Fc-gamma receptors CD32 and CD64 are the culprits," said Sridevi Devaraj, associate professor of pathology at UC Davis School of Medicine and Medical Center.