Sugars come in many forms, most of them tasting sweet. But too much of one type may leave your arteries in a bitter state.
High amounts of glucose in the blood appear to be a major culprit behind atherosclerosis, according to researchers in the Leslie & Susan Gonda (Goldschmied) Diabetes & Genetics Research Center at City of Hope.
 Rama Natarajan investigates the molecular factors linking inflammation and diabetes-related atherosclerosis. (Photo by Markie Ramirez) |
Atherosclerosis is a thickening of artery walls that narrows blood vessels and leads to heart attacks and strokes. It’s relatively common in people with diabetes.
Led by Rama Natarajan, Ph.D., professor in the Division of Diabetes, Endocrinology & Metabolism, the researchers found that exposing certain vascular cells — cells that make up blood vessels — to high levels of glucose in the lab roused an inflammatory response that could lead to atherosclerosis.
The team studied vascular smooth muscle 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 mimic diabetic conditions in the body. (To double-check their idea, in separate experiments they used a certain protein that also can simulate diabetes.)
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, and that’s when the trouble starts. Those monocytes can develop into macrophages — immune cells that under normal conditions swallow up cellular debris and invading germs — that can become embedded in blood-vessel walls. From there, the macrophages may go on to swallow up fat-related molecules called lipids, forming foam cells — the main building blocks of the plaques that develop in atherosclerosis.
The researchers found that was exactly the case. Under diabetic conditions, more monocytes stuck to vascular smooth muscle cells and embedded themselves in the blood-vessel walls. Worse, the sticky monocytes could develop much more quickly into macrophages. This eventually could lead to more foam cells and, ultimately, atherosclerosis.
The findings fit well with known facts: People with diabetes who develop atherosclerosis have more foam cells in their plaques than people who develop atherosclerosis but do not have diabetes.
The research team also found that vascular smooth muscle cells in simulated diabetic conditions produced higher levels of two key proteins involved in inflammation. These two proteins 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 a 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.
