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Adenoviral transfer of HIF-1α enhances vascular responses to critical limb ischemia in diabetic mice
- Publication Year :
- 2009
- Publisher :
- National Academy of Sciences, 2009.
-
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-1α, 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.
- Subjects :
- medicine.medical_specialty
Nitric Oxide Synthase Type III
Angiogenesis
medicine.medical_treatment
Ischemia
Neovascularization, Physiologic
Femoral artery
Revascularization
Adenoviridae
Diabetes Mellitus, Experimental
Mice
Internal medicine
medicine.artery
Diabetes mellitus
medicine
Limb perfusion
Animals
Humans
Muscle, Skeletal
Ligation
Multidisciplinary
business.industry
Extremities
Critical limb ischemia
Anatomy
Genetic Therapy
Biological Sciences
medicine.disease
Hypoxia-Inducible Factor 1, alpha Subunit
Immunohistochemistry
Femoral Artery
Cardiology
medicine.symptom
business
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....242ac93726eb6152b417e299b17dbdde