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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:608.)
© 2008 American Heart Association, Inc.

Editorials

More Sugar, Less Blood Vessels

Another Piece in the Puzzle of Increased Cardiovascular Risk in Diabetes

Christian Rask-Madsen; George L. King

From the Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, Mass.

Correspondence to George L. King, MD, Joslin Diabetes Center, Harvard Medical School, One Joslin Place, room 4504, Boston, MA 02215. E-mail george.king@joslin.harvard.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Patients with diabetes have a several-fold higher risk of cardiovascular events than people without diabetes. The susceptibility to heart failure, lower limb amputations, and other manifestations of tissue ischemia in diabetes is attributable to an increased risk of atherothrombotic disease as well as impaired neovascularization and collateral formation through arteriogenesis or angiogenesis.^1,2 Abnormal angiogenesis in diabetes, however, is complex because increased neovascularization is the hallmark of proliferative diabetic retinopathy, another major complication of the disease.

See accompanying article on page 651

The mechanisms responsible for this range of abnormal angiogenesis in different tissues in patients with diabetes are poorly understood, but relate at least in part to differential expression of hypoxia-induced angiogenic factors like vascular endothelial growth factor (VEGF). Cardiac expression of VEGF and its receptors are decreased in diabetic rats^3,4 and in patients with diabetes,³ whereas VEGF and its receptors, paradoxically, are increased in the diabetic retina, even in animal models where proliferative diabetic retinopathy does not occur.^3,5 Both insulin resistance and hyperglycemia, present in most patients with diabetes, may affect angiogenic potential. Insulin action is necessary for appropriate expression of VEGF⁶ (see Figure), and rats with obesity-associated nondiabetic insulin resistance have decreased expression of VEGF and VEGF receptors³ and decreased capillary density in the heart.⁶ Hyperglycemia itself may inhibit angiogenesis, for example through formation of advanced glycation end-products (AGE). As an example modification of (basic) fibroblast growth factor-2 (FGF2) by AGE,⁷ as shown by several independent groups, inhibits its angiogenic action. Even though many studies have shown . . . [Full Text of this Article]

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