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Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery.

Publication ,  Journal Article
Hoshijima, M; Ikeda, Y; Iwanaga, Y; Minamisawa, S; Date, M-O; Gu, Y; Iwatate, M; Li, M; Wang, L; Wilson, JM; Wang, Y; Ross, J; Chien, KR
Published in: Nat Med
August 2002

The feasibility of gene therapy for cardiomyopathy, heart failure and other chronic cardiac muscle diseases is so far unproven. Here, we developed an in vivo recombinant adeno-associated virus (rAAV) transcoronary delivery system that allows stable, high efficiency and relatively cardiac-selective gene expression. We used rAAV to express a pseudophosphorylated mutant of human phospholamban (PLN), a key regulator of cardiac sarcoplasmic reticulum (SR) Ca(2+) cycling in BIO14.6 cardiomyopathic hamsters. The rAAV/S16EPLN treatment enhanced myocardial SR Ca(2+) uptake and suppressed progressive impairment of left ventricular (LV) systolic function and contractility for 28-30 weeks, thereby protecting cardiac myocytes from cytopathic plasma-membrane disruption. Low LV systolic pressure and deterioration in LV relaxation were also largely prevented by rAAV/S16EPLN treatment. Thus, transcoronary gene transfer of S16EPLN via rAAV vector is a potential therapy for progressive dilated cardiomyopathy and associated heart failure.

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Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

August 2002

Volume

8

Issue

8

Start / End Page

864 / 871

Location

United States

Related Subject Headings

  • Sequence Alignment
  • Sarcoplasmic Reticulum
  • Myocardium
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Liver
  • Immunology
  • Humans
  • Hemodynamics
 

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Hoshijima, M., Ikeda, Y., Iwanaga, Y., Minamisawa, S., Date, M.-O., Gu, Y., … Chien, K. R. (2002). Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med, 8(8), 864–871. https://doi.org/10.1038/nm739
Hoshijima, Masahiko, Yasuhiro Ikeda, Yoshitaka Iwanaga, Susumu Minamisawa, Moto-o Date, Yusu Gu, Mitsuo Iwatate, et al. “Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery.Nat Med 8, no. 8 (August 2002): 864–71. https://doi.org/10.1038/nm739.
Hoshijima M, Ikeda Y, Iwanaga Y, Minamisawa S, Date M-O, Gu Y, et al. Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med. 2002 Aug;8(8):864–71.
Hoshijima, Masahiko, et al. “Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery.Nat Med, vol. 8, no. 8, Aug. 2002, pp. 864–71. Pubmed, doi:10.1038/nm739.
Hoshijima M, Ikeda Y, Iwanaga Y, Minamisawa S, Date M-O, Gu Y, Iwatate M, Li M, Wang L, Wilson JM, Wang Y, Ross J, Chien KR. Chronic suppression of heart-failure progression by a pseudophosphorylated mutant of phospholamban via in vivo cardiac rAAV gene delivery. Nat Med. 2002 Aug;8(8):864–871.

Published In

Nat Med

DOI

ISSN

1078-8956

Publication Date

August 2002

Volume

8

Issue

8

Start / End Page

864 / 871

Location

United States

Related Subject Headings

  • Sequence Alignment
  • Sarcoplasmic Reticulum
  • Myocardium
  • Mutation
  • Molecular Sequence Data
  • Mice
  • Liver
  • Immunology
  • Humans
  • Hemodynamics