Therapeutic angiogenesis for critical limb ischemia: invited commentary.
Lower extremity arterial occlusive disease results in tissue ischemia of the legs and is relatively common in the elderly. Clinically, it may be asymptomatic, cause muscle pain during exercise, or progress to a severe degree of ischemia that may result in limb loss. Although bypass surgery and angioplasty have increased the rate of limb salvage in these patients, amputation of the affected limb remains a common outcome for many patients. Therapeutic angiogenesis is the administration of angiogenic factors, or genes encoding these factors, to promote neovascularization and thereby increase blood flow to the ischemic leg. We have developed an animal model of hindlimb ischemia in which to study therapeutic angiogenesis. We chose nitric oxide as the angiogenic factor for our experiments because of its ability to induce angiogenesis, vasodilation, and inhibit inflammation. In this review, we will discuss our experience with our model of hindlimb ischemia, as well as discuss our results of gene therapy for therapeutic angiogenesis using nitric oxide.
Messina
Louis M
LM
Division of Vascular Surgery, Department of Surgery, University of California at San Francisco M-488, 505 Parnassus Avenue, San Francisco, CA 94143-0222, USA. messinal@surgery.ucsf.edu
Brevetti
Lucy S
LS
Chang
David S
DS
Paek
Robert
R
Sarkar
Rajabrata
R
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D005121:Extremities / Q000098:blood supply*; D022761:Gene Transfer, Horizontal; D015316:Genetic Therapy; D006801:Humans; D007511:Ischemia / Q000628:therapy*; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052250:Nitric Oxide Synthase Type III; D012039:Regional Blood Flow
D009569:Nitric Oxide; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III