Editors' ChoicePeripheral Vascular Disease

Reducing the Effects of Diabetes

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Science Translational Medicine  11 Nov 2009:
Vol. 1, Issue 6, pp. 6ec23
DOI: 10.1126/scitranslmed.3000562

Those with diabetes are at risk for a severe form of peripheral vascular disease—critical limb ischemia—in which blood flow is too weak to maintain tissue viability in the legs or feet. Resulting from hardening and narrowing of the arteries, this disease often causes severe pain, sores that will not heal, and gangrene. It is also the primary reason for amputations, at least those not related to physical trauma. Because patients with critical limb ischemia are often not good candidates for current treatments, such as surgery to restore vascularization, therapies that promote the growth of new blood vessels would be welcome. Toward that end, Sarkar et al. investigated whether hypoxia-inducible factor 1 (HIF-1), a transcriptional activator that regulates responses to an inadequate blood supply and insufficient oxygen, might be of therapeutic value in peripheral ischemia induced in a mouse model of type 2 diabetes. These researchers first showed that, relative to controls, the diabetic mice had poor vascular responses to ligation of a large artery in the leg, in that the return of blood flow was reduced and tissue death was increased over a period of several weeks. They next tested the effects of injecting an adenovirus encoding a constitutively active HIF-1 subunit into the region once served by the ligated artery and found that this treatment increased circulating cells that promote vascularization, increased vessel density, and reduced tissue death. These results suggest that such therapy might warrant a trial in diabetic patients with critical limb ischemia.

K. Sarkar et al., Adenoviral transfer of HIF-1α enhances vascular responses to critical limb ischemia in diabetic mice. Proc. Natl. Acad. Sci. U.S.A. 106, 18769–18774 (2009). [Abstract]

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