A new paradigm for the progression of advanced heart failure.

DOI Web Site PubMed 41 References
  • KAWADA Tomie
    Division of Pharmacy, Niigata University Medical & Dental Hospital
  • NAKAZAWA Mikio
    Department of Basic Biochemical Information, School of Health Science, Faculty of Medicine, Niigata University
  • TOYO-OKA Teruhiko
    Department of Pathophysiology and Internal Medicine, University of Tokyo

Bibliographic Information

Other Title
  • 心不全の重症化機構－その新しい概念－
  • シンフゼン ノ ジュウショウカ キコウ ソノ アタラシイ ガイネン

Search this article

Abstract

To clarify the precise mechanism for the progression of advanced heart failure (AdHF), we assessed the scheme in two HF models, using (I) TO-2 strain hamsters sharing common genetic and clinical features to human families with the δ-sarcoglycan (SG) gene mutation and (II) administration of a high-dose (HD) of isoproterenol (Isp) to normal rats. δ-SG is a component in dystrophin (Dys)-related proteins that stabilize the sarcolemma (SL) during repeated heart beats. In TO-2, we followed time course of hemodynamics, immunostaining and Western blotting of Dys and in situ SL permeability by Evans blue uptake with or without the gene therapy. Dys was age-dependently translocated from the SL to myoplasm (MP) where the SL instability accompanied the fragmention of Dys. By gene therapy to supplement the normal δ-SG gene in hearts in vivo, we found that Dys translocation was selectively improved in cardiomyocytes expressing the δ-SG transgene, where the SL fragility was ameliorated. Most importantly, the survival period of the animals was prolonged. Furthermore, Dys but not δ-SG was also time-dependently shifted with a HD of Isp from the SL to MP and fragmented, while δ-SG was preserved intact. We present a novel paradigm that disruption of Dys, but not δ-SG per se, leads to AdHF irrespective of hereditary or acquired origin.<br>

Journal

References(41)*help

See more

Related Projects

See more

Keywords

Details 詳細情報について

Report a problem

Back to top