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Neovascularization of ischemic tissues by gene delivery of the extracellular matrix protein Del-1.
Zhong, Jingping; Eliceiri, Brian; Stupack, Dwayne; Penta, Kalyani; Sakamoto, Gordon; Quertermous, Thomas; Coleman, Mike; Boudreau, Nancy; Varner, Judith A.
Affiliation
  • Zhong J; Comprehensive Cancer Center, University of California, San Diego, La Jolla, California 92093-0912, USA.
J Clin Invest ; 112(1): 30-41, 2003 Jul.
Article in En | MEDLINE | ID: mdl-12840057
ABSTRACT
The ECM protein Del-1 is one of several novel ECM proteins that accumulate around angiogenic blood vessels in embryonic and tumor tissue and promote angiogenesis in the absence of exogenous growth factors. Del-1 expressed in mouse or rabbit ischemic hind-limb muscle by gene transfer rapidly promotes new blood vessel formation and restores muscle function. This angiogenic ECM protein initiates angiogenesis by binding to integrin alphavbeta5 on resting endothelium, thereby resulting in expression of the transcription factor Hox D3 and integrin alphavbeta3. Hox D3 converts resting endothelium to angiogenic endothelium by inducing expression of proangiogenic molecules such as integrin alphavbeta3. These findings provide evidence for an angiogenic switch that can be initiated in the absence of exogenous growth factors and indicate that the angiogenic matrix protein Del-1 may be a useful tool for the therapy of ischemic disease.
Subject(s)

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Therapy / Carrier Proteins / Neovascularization, Physiologic / DNA-Binding Proteins / Ischemia Limits: Animals Language: En Journal: J Clin Invest Year: 2003 Document type: Article Affiliation country: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Genetic Therapy / Carrier Proteins / Neovascularization, Physiologic / DNA-Binding Proteins / Ischemia Limits: Animals Language: En Journal: J Clin Invest Year: 2003 Document type: Article Affiliation country: United States