Low levels of vitamin D are known to nearly double the risk of cardiovascular disease in patients with diabetes, and School of Medicine researchers now say they know why.
They have found that diabetics deficient in vitamin D can’t process cholesterol normally, so it builds up in their blood vessels, increasing the risk of heart attack and stroke. The new research has identified a mechanism linking low vitamin D levels to heart disease risk and may lead to ways to fix the problem simply by increasing levels of vitamin D.
Bernal-Mizrachi
“Vitamin D inhibits the uptake of cholesterol by cells called macrophages,” said principal investigator Carlos Bernal-Mizrachi, M.D., assistant professor of medicine and of cell biology and physiology. “When people are deficient in vitamin D, the macrophage cells eat more cholesterol, and they can’t get rid of it. The macrophages get clogged with cholesterol and become what scientists call foam cells, one of the earliest markers of atherosclerosis.”
Macrophages are dispatched by the immune system in response to inflammation and often are activated by diseases such as diabetes. Bernal-Mizrachi and his colleagues say that in diabetic patients with inadequate vitamin D, macrophages become loaded with cholesterol and eventually stiffen blood vessels and block blood flow.
Bernal-Mizrachi studied macrophage cells taken from people with and without diabetes and with and without vitamin D deficiency. His team, led by research assistants Jisu Oh and Sherry Weng, M.D., exposed the cells to cholesterol and to high or low vitamin D levels. When vitamin D levels were low in the culture dish, macrophages from diabetic patients were much more likely to become foam cells.
In the Aug. 25 issue of the journal Circulation, the team reports that vitamin D regulates signaling pathways linked both to uptake and to clearance of cholesterol in macrophages.
“Cholesterol is transported through the blood attached to lipoproteins such as LDL, the ‘bad’ cholesterol,” Bernal-Mizrachi said. “As it is stimulated by oxygen radicals in the vessel wall, LDL becomes oxidated, and macrophages eat it uncontrollably. LDL cholesterol then clogs the macrophages, and that’s how atherosclerosis begins.”
That process accelerates when a person is deficient in vitamin D, and people with type 2 diabetes are very likely to have this deficiency. Worldwide, about 1 billion people have insufficient vitamin D levels. Women with type 2 diabetes are about a third more likely to have low vitamin D than women of the same age without diabetes.
When human macrophages are placed in an environment with plenty of vitamin D, their uptake of cholesterol is suppressed, and they don’t become foam cells. Bernal-Mizrachi said it may be possible to slow or reverse the development of atherosclerosis in patients with diabetes by helping them regain adequate vitamin D levels.
He is studying diabetics who are both deficient in vitamin D and have high blood pressure to learn whether replacing vitamin D will lower blood pressure and improve blood flow. For this study, Bernal-Mizrachi is recruiting patients with type 2 diabetes and high blood pressure ages 30-80 who are not taking insulin to control their blood sugar.
For more information, contact mpetty@DOM.wustl.edu or call 362-0934.