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S100A1 Gene Therapy in Small and Large Animals

  • Patrick MostEmail author
  • Philip Raake
  • Christophe Weber
  • Hugo A. Katus
  • Sven T. Pleger
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 963)

Abstract

Myocardial in vivo gene delivery is a valuable technique to investigate the relevance of a protein of interest on cardiac contractile function, hypertrophy, and energy state in healthy animals as well as in a variety of models of cardiovascular disease. Rodent models are used to screen effects and to investigate molecular mechanisms, while large animal models, more closely reflecting human anatomy, physiology, and function, are inevitable for translational therapeutic approaches. The gene of interest, whose expression is driven by a non-cardioselective or cardioselective promotor is cloned into a viral vector. This vehicle is then delivered using an appropriate administration route to target the heart and to achieve efficient protein expression in myocardium.

Here we describe myocardial gene therapy in small and large animal models of postischemic heart failure used to reveal the positive inotrope, antihypertrophic, and pro-energetic action of the small calcium sensor protein S100A1.

Key words

S100A1 Calcium EF-hand Myocardial gene therapy Retroinfusion Antegrade ­delivery Adenovirus Adeno-associated virus Efficacy Cardioselective 

Notes

Acknowledgments

This work was supported by NIH grants: R01HL92130 and R01HL92130-02S1 (P.M.); Deutsche Forschungsgemeinschaft: 562/1-1 (P.M. and S.T.P.); and the Bundesministerium für Bildung und Forschung: 01GU0527 (P.M., H.A.K.); the Pennsylvania-Delaware Affiliate of the American Heart Association (S.T.P.); the Lilly-Stipendium of the Deutsche Gesellschaft für Kardiologie (S.T.P.).

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Patrick Most
    • 1
    Email author
  • Philip Raake
    • 2
  • Christophe Weber
    • 1
  • Hugo A. Katus
    • 2
  • Sven T. Pleger
    • 1
  1. 1.Department of Internal Medicine III, Center for Molecular and Translational CardiologyUniversity of HeidelbergHeidelbergGermany
  2. 2.Department of Internal Medicine IIIUniversity of HeidelbergHeidelbergGermany

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