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Adenoviral transfer of HIF-1alpha enhances vascular responses to critical limb ischemia in diabetic mice.


ABSTRACT: Diabetes is a major risk factor for ischemic disease. Treatment options for diabetic patients with peripheral arterial disease when revascularization is not possible are limited, resulting in a high incidence of limb amputation. We evaluated the therapeutic potential of AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, in a diabetic model of critical limb ischemia. Diabetic db/db and nondiabetic db/+ mice were subjected to unilateral femoral artery ligation. Limb perfusion, tissue viability, and motor function were more severely impaired in db/db mice. Intramuscular injection of AdCA5 into the ischemic limb of db/db mice increased the recovery of limb perfusion and function, reduced tissue necrosis, rescued the diabetes-associated impairment of circulating angiogenic cells, enhanced endothelial nitric oxide synthase activation, and increased vessel density and luminal area in the ischemic limb.

SUBMITTER: Sarkar K 

PROVIDER: S-EPMC2774037 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature

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Adenoviral transfer of HIF-1alpha enhances vascular responses to critical limb ischemia in diabetic mice.

Sarkar Kakali K   Fox-Talbot Karen K   Steenbergen Charles C   Bosch-Marcé Marta M   Semenza Gregg L GL  

Proceedings of the National Academy of Sciences of the United States of America 20091019 44


Diabetes is a major risk factor for ischemic disease. Treatment options for diabetic patients with peripheral arterial disease when revascularization is not possible are limited, resulting in a high incidence of limb amputation. We evaluated the therapeutic potential of AdCA5, an adenovirus encoding a constitutively active form of HIF-1alpha, in a diabetic model of critical limb ischemia. Diabetic db/db and nondiabetic db/+ mice were subjected to unilateral femoral artery ligation. Limb perfusio  ...[more]

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