Genetic engineering and therapy for inherited and acquired cardiomyopathies

Sharlene Day, Jennifer Davis, Margaret Westfall, Joseph M. Metzger

Research output: Chapter in Book/Report/Conference proceedingConference contribution

4 Scopus citations

Abstract

The cardiac myofilaments consist of a highly ordered assembly of proteins that collectively generate force in a calcium-dependent manner. Defects in myofilament function and its regulation have been implicated in various forms of acquired and inherited human heart disease. For example, during cardiac ischemia, cardiac myocyte contractile performance is dramatically downregulated due in part to a reduced sensitivity of the myofilaments to calcium under acidic pH conditions. Over the last several years, the thin filament regulatory protein, troponin I, has been identified as an important mediator of this response. Mutations in troponin I and other sarcomere genes are also linked to several distinct inherited cardiomyopathic phenotypes, including hypertrophic, dilated, and restrictive cardiomyopathies. With the cardiac sarcomere emerging as a central player for such a diverse array of human heart diseases, genetic-based strategies that target the myofilament will likely have broad therapeutic potential. The development of safe vector systems for efficient gene delivery will be a critical hurdle to overcome before these types of therapies can be successfully applied. Nonetheless, studies focusing on the principles of acute genetic engineering of the sarcomere hold value as they lay the essential foundation on which to build potential gene-based therapies for heart disease.

Original languageEnglish (US)
Title of host publicationInteractive and Integrative Cardiology
PublisherBlackwell Publishing Inc
Pages437-450
Number of pages14
ISBN (Print)1573316512, 9781573316514
DOIs
StatePublished - Oct 2006

Publication series

NameAnnals of the New York Academy of Sciences
Volume1080
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632

Keywords

  • Gene delivery
  • Gene-based therapies
  • Myofilament regulation
  • Sarcomere
  • Troponin I

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