Editors' ChoiceDiabetes

Beating Heart Disease in Diabetes

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Science Translational Medicine  22 Sep 2010:
Vol. 2, Issue 50, pp. 50ec146
DOI: 10.1126/scitranslmed.3001692

The elevated blood glucose levels that diabetic patients contend with on a daily basis also predispose them to prematurely developing heart disease. A major cause of heart disease is the formation of fatty lesions (atherosclerotic plaques) that bind to and damage the endothelial layer of blood vessels, eventually blocking them and preventing blood flow. These plaques contain oxidized low-density lipoproteins and peroxidized lipids as well as foamy macrophages and other cells. Glucose-mediated oxidative stress and lipoprotein oxidation may contribute to the premature development of atherosclerosis and heart disease in diabetic patients. Several animal studies have shown that apolipoprotein A-I (apoA-I) can slow or even prevent the buildup of these lesions in blood vessels, thus protecting against vascular disease. Now, Morgantini et al. demonstrate that an apoA-I mimetic called D-4F interferes with the formation of these plaques in diabetic mice, providing a new approach for preventing heart disease in patients with diabetes.

The investigators created an animal model of type I diabetes by treating engineered mice with streptozotocin, a drug that damages the pancreas. One group of these diabetic animals received D-4F in their drinking water for 8 weeks, whereas a control group did not. The animals were then killed, and the size and content of atherosclerotic plaques in the aorta were measured. The authors discovered that D-4F–treated diabetic mice had smaller plaques with a lower lipid content and fewer foamy macrophages than did control mice. Treated animals also showed reduced oxidized fatty acids and arachidonic acid (a fatty acid precursor) in the liver as compared with that of control mice. D-4F mediated these beneficial effects without altering glucose, insulin, or lipoprotein-cholesterol complexes in the plasma. The authors propose that D-4F removes oxidized lipids from lipoproteins in plaques, resulting in reduced tissue inflammation and fewer macrophages migrating into these vascular lesions.

Premature heart disease is a leading cause of death among diabetic patients. Thus, apoA-I mimetics may be a welcome addition to the drug armamentarium for slowing or even preventing plaque formation and premature heart disease in individuals with diabetes.

C. Morgantini et al., ApoA-I mimetic peptides prevent atherosclerosis development and reduce plaque inflammation in a mouse model of diabetes. Diabetes 8 September 2010 (10.2337/db10-0844). [Abstract]

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