In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis

Djamel Lebeche; Roger Kaprielian; Federica Del Monte; Gordon Tomaselli; Judith K. Gwathmey; Arnold Schwartz; Roger J. Hajjar

doi:10.1161/01.CIR.0000148176.33730.3F

In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis

Djamel Lebeche, Roger Kaprielian, Federica Del Monte, Gordon Tomaselli, Judith K. Gwathmey, Arnold Schwartz, Roger J. Hajjar

School of Medicine

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Background - Prolongation of the action potential duration (APD) and decreased transient outward K⁺ current (I_to] have been consistently observed in cardiac hypertrophy. The relation between electrical remodeling and cardiac hypertrophy in vivo is unknown. Methods and Results - We studied rat hearts subjected to pressure overload by surgical ascending aortic stenosis (AS) and simultaneously infected these hearts with an adenovirus carrying either the Kv4.3 gene (Ad.Kv4.3) or the β-galactosidase gene (Ad.β-gal). I_to density was reduced and APD₅₀ was prolonged (Pto density, and shorten APD₅₀ by 1.6-fold, 5.3-fold, and 3.6-fold, respectively (Pto, APD prolongation, and cardiac hypertrophy occur early after AS, and in vivo gene transfer of Kv4.3 can restore these electrical parameters and abrogate the hypertrophic response via the calcineurin pathway.

Original language	English (US)
Pages (from-to)	3435-3443
Number of pages	9
Journal	Circulation
Volume	110
Issue number	22
DOIs	https://doi.org/10.1161/01.CIR.0000148176.33730.3F
State	Published - Nov 30 2004

Keywords

Gene therapy
Hypertrophy
Ion channels
Potassium
Stenosis

ASJC Scopus subject areas

Physiology
Cardiology and Cardiovascular Medicine

Access to Document

10.1161/01.CIR.0000148176.33730.3F

Cite this

@article{9983263c605048978ed747c0b06896b9,

title = "In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis",

abstract = "Background - Prolongation of the action potential duration (APD) and decreased transient outward K+ current (Ito] have been consistently observed in cardiac hypertrophy. The relation between electrical remodeling and cardiac hypertrophy in vivo is unknown. Methods and Results - We studied rat hearts subjected to pressure overload by surgical ascending aortic stenosis (AS) and simultaneously infected these hearts with an adenovirus carrying either the Kv4.3 gene (Ad.Kv4.3) or the β-galactosidase gene (Ad.β-gal). Ito density was reduced and APD50 was prolonged (Pto density, and shorten APD50 by 1.6-fold, 5.3-fold, and 3.6-fold, respectively (Pto, APD prolongation, and cardiac hypertrophy occur early after AS, and in vivo gene transfer of Kv4.3 can restore these electrical parameters and abrogate the hypertrophic response via the calcineurin pathway.",

keywords = "Gene therapy, Hypertrophy, Ion channels, Potassium, Stenosis",

author = "Djamel Lebeche and Roger Kaprielian and {Del Monte}, Federica and Gordon Tomaselli and Gwathmey, {Judith K.} and Arnold Schwartz and Hajjar, {Roger J.}",

year = "2004",

month = nov,

day = "30",

doi = "10.1161/01.CIR.0000148176.33730.3F",

language = "English (US)",

volume = "110",

pages = "3435--3443",

journal = "Circulation",

issn = "0009-7322",

publisher = "Lippincott Williams and Wilkins",

number = "22",

}

TY - JOUR

T1 - In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis

AU - Lebeche, Djamel

AU - Kaprielian, Roger

AU - Del Monte, Federica

AU - Tomaselli, Gordon

AU - Gwathmey, Judith K.

AU - Schwartz, Arnold

AU - Hajjar, Roger J.

PY - 2004/11/30

Y1 - 2004/11/30

N2 - Background - Prolongation of the action potential duration (APD) and decreased transient outward K+ current (Ito] have been consistently observed in cardiac hypertrophy. The relation between electrical remodeling and cardiac hypertrophy in vivo is unknown. Methods and Results - We studied rat hearts subjected to pressure overload by surgical ascending aortic stenosis (AS) and simultaneously infected these hearts with an adenovirus carrying either the Kv4.3 gene (Ad.Kv4.3) or the β-galactosidase gene (Ad.β-gal). Ito density was reduced and APD50 was prolonged (Pto density, and shorten APD50 by 1.6-fold, 5.3-fold, and 3.6-fold, respectively (Pto, APD prolongation, and cardiac hypertrophy occur early after AS, and in vivo gene transfer of Kv4.3 can restore these electrical parameters and abrogate the hypertrophic response via the calcineurin pathway.

AB - Background - Prolongation of the action potential duration (APD) and decreased transient outward K+ current (Ito] have been consistently observed in cardiac hypertrophy. The relation between electrical remodeling and cardiac hypertrophy in vivo is unknown. Methods and Results - We studied rat hearts subjected to pressure overload by surgical ascending aortic stenosis (AS) and simultaneously infected these hearts with an adenovirus carrying either the Kv4.3 gene (Ad.Kv4.3) or the β-galactosidase gene (Ad.β-gal). Ito density was reduced and APD50 was prolonged (Pto density, and shorten APD50 by 1.6-fold, 5.3-fold, and 3.6-fold, respectively (Pto, APD prolongation, and cardiac hypertrophy occur early after AS, and in vivo gene transfer of Kv4.3 can restore these electrical parameters and abrogate the hypertrophic response via the calcineurin pathway.

KW - Gene therapy

KW - Hypertrophy

KW - Ion channels

KW - Potassium

KW - Stenosis

UR - http://www.scopus.com/inward/record.url?scp=10044227180&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=10044227180&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000148176.33730.3F

DO - 10.1161/01.CIR.0000148176.33730.3F

M3 - Article

C2 - 15557376

AN - SCOPUS:10044227180

SN - 0009-7322

VL - 110

SP - 3435

EP - 3443

JO - Circulation

JF - Circulation

IS - 22

ER -

In vivo cardiac gene transfer of Kv4.3 abrogates the hypertrophic response in rats after aortic stenosis

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this