HOUSTON -- (June 16, 2009) -- Cells called monocytes that sport a cellular receptor known as beta-2 integrin CD11c begin to accumulate lipids while still circulating in the blood stream, accelerating processes that lead to atherosclerosis, or hardening of the arteries, before they even stick to the artery wall, said researchers at Baylor College of Medicine in a report that appears in the current edition of the journal Circulation.
"We've known that CD11c plays a key role in white blood cell adhesion to the lining of the arterial wall, a process that has critical contribution to development of atherosclerosis," said Dr. Christie Ballantyne, interim chief of cardiology at BCM. "However, the processes, how it happens and whether CD11c is involved in atherosclerosis development, are not fully understood."
It was believed that lipids were picked up by white blood cells after the white blood cells had adhered to the arterial wall, and that CD11c was responsible for this action. So, to pin point exactly how, researchers bred mice expressing CD11c and some that did not.
When the mice expressing CD11c were fed high fat diets, researchers found there was a higher proportion of CD11c monocytes in circulation. The white blood cells were absorbing lipids before becoming adherant to the arterial wall. Once the cells begin to accumulate the lipids they express more CD11c on their surface and become what are known as foam cells. This process then activates the cells, making the cells "stickier" to the vessel wall.
"It was believed these foam cells begin taking up lipids after adhesion but they are actually taking them up during circulation in this mouse model of hypercholesterolemia which means they are being activated before entering the vessel walls," said Dr. Huaizhu Wu, assistant professor of medicine - atherosclerosis and vascular medicine, and lead author of the study.
"We think that means the foam cells can go into the arterial wall and into the skin which is why some people with severe hyperlipidemia also developed xanthomas," said Ballantyne, who is also chief of the section of atherosclerosis and vascular medicine and professor of medicine at BCM.
Xanthomas are a collection of foam cells and cholesterol in the skin and tendons seen in people with very high cholesterol levels. For those mice deficient in CD11c, researchers saw a decrease in monocyte firm adhesion. There was also a decrease in atherosclerosis development.
"This could lead to a target for future treatments, but the obvious treatment is to lower the lipids so there won't be anything to be absorbed in the first place," Ballantyne said. "However, this particular monocyte is believed to play a role in atherosclerosis and metabolic disease as well so understanding how it works is important to understanding how the diseases develop."
Funding for this study came from the National Institutes of Health, the American Heart Association, the U.S. Department of Agriculture, and a Howard Hughes Medical Institute.
Others who took part in the study include, Dr. Xiao-Yuan Dai Perrard, section of atherosclerosis and vascular medicine at BCM and center for cardiovascular disease prevention, the Methodist DeBakey Heart and Vascular Center; Ruidong Ma, section of thrombosis research at BCM; Dr. Antoni Paul division of diabetes, endocrinology, and metabolism at BCM; Dr. C. Wayne Smith and Dr. Alan R. Burns department of medicine, and section of leukocyte biology, department of pediatrics at BCM; R. Michael Gower and Scott I. Simon, department of bioengineering, University of California at Davis; Dr. Hong Wang, department of pharmacology, Temple University School of Medicine; Dr. Daniel C. Bullard, department of genetics, research division, University of Alabama at Birmingham. Ballantyne is also with the center for cardiovascular disease prevention at the Methodist DeBakey Heart and Vascular Center.
For more information on basic science research at Baylor College of Medicine, please go to www.bcm.edu/fromthelab.
Contact: Graciela Gutierrez, 713-798-4710, email@example.com
Source: Baylor College of Medicine