High blood-sugar levels commonly found in people with diabetes appear to promote atherosclerosis, according to researchers in the Leslie & Susan Gonda (Goldschmied) Diabetes & Genetics Research Center. The findings could explain why the artery-blocking disease is common in people with diabetes.
 Rama Natarajan investigates the molecular factors linking inflammation and diabetes-related atherosclerosis. (Photo by Markie Ramirez) |
Led by Rama Natarajan, Ph.D., professor in the Division of Diabetes, Endocrinology & Metabolism, the researchers found that exposing certain vascular cells to high levels of glucose in the lab provoked an inflammatory response that could lead to atherosclerosis. Atherosclerosis is a thickening of artery walls that narrows blood vessels and leads to heart attacks and strokes.
The team, which published the findings in a recent issue of the American Journal of Physiology - Heart and Circulatory Physiology, performed the study using vascular smooth muscles cells, the cells that make up most of the walls of blood vessels. They treated these cells with a high concentration of the sugar glucose to simulate diabetic conditions. In separate experiments, they also applied a protein similar to advanced glycation end products to mimic diabetic conditions.
Advanced glycation end products are modified proteins, DNA and other cellular molecules that can arise when glucose levels are high.
The team found that white blood cells called monocytes were much more likely to stick to the vascular cells under the diabetic conditions than under normal conditions. Monocytes can develop into macrophages that, when embedded in blood-vessel walls, can go on to engulf fat-related molecules called lipids and form foam cells.
Foam cells are the main component of the plaques that develop in atherosclerosis. People with diabetes who develop atherosclerosis have more foam cells in their plaques than people who develop atherosclerosis but do not have diabetes.
The researchers found that the diabetic conditions not only provoked more monocytes to stick themselves to vascular smooth muscle cells and embed in the blood-vessel walls, but the adherent monocytes also could develop much faster into macrophages. This could eventually lead to enhanced foam cell formation and atherosclerosis.
The research team also found that vascular smooth muscle cells in simulated diabetic conditions produced increased amounts of inflammatory proteins called chemokines. Specifically, they produced two chemokines called monocyte chemoattractant protein-1 and fractalkine. These two chemokines attract monocytes to vascular smooth muscle cells and into the vessel wall.
“High blood glucose creates an ideal environment for promoting vascular inflammation and atherosclerosis, which could explain the significantly accelerated rates of vascular disease observed in people with diabetes,” said Natarajan.
When atherosclerosis occurs in an artery that supplies blood to the heart or the brain, it can lead to heart disease or strokes. In extreme cases, an atherosclerotic plaque can rupture, blocking blood-flow altogether and causing a sudden heart attack. People with diabetes have three- to four-fold greater risk of dying from causes related to cardiovascular diseases and strokes.
Natarajan hopes to uncover more details about the process of atherosclerosis and plaque formation in people with diabetes in future studies.
Other City of Hope researchers on the current study include Li Meng, M.D., Jehyun Park, Ph.D., Qiangjun Cai, M.D., Ph.D., Linda Lanting, and Marpadga A. Reddy, Ph.D.
The research, published Dec. 11, 2009, was supported by grants from the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and the American Diabetes Association.
