Abstract

This application is for continued funding to develop optimal transduction efficiency in skeletal muscle capillary endothelium and muscle fibers during vascular isolation of the hindlimb, and to determine the efficacy of these approaches to achieve therapeutic concentrations of appropriate recombinant proteins (VEGF, eNOS and dystrophin) in animal models, and finally to determine whether this approach can be accomplished using a catheter-based technique. In preliminary data from this group, high transduction efficiencies have been obtained without evidence of muscle injury or necrosis. These experiments are directed at optimizing the methods rather than at obtaining a therapeutic result.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL051184-05
Application #
2029007
Study Section
Special Emphasis Panel (ZRG7-SAT (01))
Project Start
1994-04-09
Project End
2000-07-31
Budget Start
1997-08-01
Budget End
1998-07-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Surgery
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Chang, David S; Su, Hua; Tang, Gale L et al. (2003) Adeno-associated viral vector-mediated gene transfer of VEGF normalizes skeletal muscle oxygen tension and induces arteriogenesis in ischemic rat hindlimb. Mol Ther 7:44-51
Brevetti, Lucy S; Chang, David S; Tang, Gale L et al. (2003) Overexpression of endothelial nitric oxide synthase increases skeletal muscle blood flow and oxygenation in severe rat hind limb ischemia. J Vasc Surg 38:820-6
Messina, Louis M; Brevetti, Lucy S; Chang, David S et al. (2002) Therapeutic angiogenesis for critical limb ischemia: invited commentary. J Control Release 78:285-94
Paek, Robert; Chang, David S; Brevetti, Lucy S et al. (2002) Correlation of a simple direct measurement of muscle pO(2) to a clinical ischemia index and histology in a rat model of chronic severe hindlimb ischemia. J Vasc Surg 36:172-9
Brevetti, Lucy S; Chang, David S; Sarkar, Rajabrata et al. (2002) Effect of adenoviral titer and instillation pressure on gene transfer efficiency to arterial and venous grafts ex-vivo. J Vasc Surg 36:263-70
Brevetti, L S; Paek, R; Brady, S E et al. (2001) Exercise-induced hyperemia unmasks regional blood flow deficit in experimental hindlimb ischemia. J Surg Res 98:21-6
Brevetti, L S; Sarkar, R; Chang, D S et al. (2001) Administration of adenoviral vectors induces gangrene in acutely ischemic rat hindlimbs: role of capsid protein-induced inflammation. J Vasc Surg 34:489-96
Furukawa, L; Brevetti, L S; Brady, S E et al. (2000) Adenoviral-mediated gene transfer of ICP47 inhibits major histocompatibility complex class I expression on vascular cells in vitro. J Vasc Surg 31:558-66
Zelenock, J A; Welling, T H; Sarkar, R et al. (1997) Improved retroviral transduction efficiency of vascular cells in vitro and in vivo during clinically relevant incubation periods using centrifugation to increase viral titers. J Vasc Surg 26:119-27
Welling, T H; Huber, T S; Messina, L M et al. (1996) Tissue plasminogen activator increases canine endothelial cell proliferation rate through a plasmin-independent, receptor-mediated mechanism. J Surg Res 66:36-42

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