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Gene Therapy Techniques for the Delivery of Endothelial Nitric Oxide Synthase to the Lung for Pulmonary Hypertension

  • W. Deng
  • T.J. Bivalacqua
  • H.C. Champion
  • W.J. Hellstrom
  • Subramanyam N. Murthy
  • Philip J. Kadowitz
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 610)

Abstract

Pulmonary hypertension (PH) is a serious, often fatal disease characterized by remodeling of the pulmonary vascular bed, increased pulmonary arterial pressure, and right heart failure. The increased vascular resistance in the pulmonary circulation is due to structural changes and increased vasoconstrictor tone. Although current therapies have prolonged survival, the long-term outcome is not favorable. Nitric oxide (NO) is synthesized by endothelial nitric oxide synthase (eNOS) and is important in regulating vascular resistance and in vascular remodeling in the lung. NO deficiency due to endothelial dysfunction plays an important role in the pathogenesis of PH. Therefore, local eNOS gene delivery to the lung is a promising approach for the treatment of PH. Adenoviral-mediated in vivo gene therapy and adult stem cell-based ex vivo gene therapy are two attractive current gene therapies for the treatment of cardiovascular and pulmonary diseases. In this chapter we describe the use of two gene transfer techniques, i.e., adenoviral gene transfer of eNOS and eNOS gene-modified rat marrow stromal cells, for eNOS gene delivery to the lung of laboratory animals for the treatment of PH.

Key words

Gene therapy pulmonary hypertension endothelial nitric oxide synthase adenovirus marrow stromal cells mesenchymal stem cells lung 

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Copyright information

© Humana Press, a part of Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • W. Deng
    • 1
  • T.J. Bivalacqua
    • 1
    • 2
  • H.C. Champion
    • 3
  • W.J. Hellstrom
    • 4
  • Subramanyam N. Murthy
    • 5
  • Philip J. Kadowitz
    • 1
  1. 1.Departments of PharmacologyTulane University Health Sciences CenterNew OrleansUSA
  2. 2.Department of UrologyJohns Hopkins HospitalBaltimoreUSA
  3. 3.Department of Medicine UniversityPittsburgUSA
  4. 4.Department of UrologyTulane University Health Sciences CenterNew OrleansUSA
  5. 5.Departments of Medicine and PharmacologyTulane University School of MedicineNew OrleansUSA

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