Targeted expression of receptor-associated late transducer inhibits maladaptive hypertrophy via blocking epidermal growth factor receptor signaling

Jun Cai, Fang Fang Yi, Long Yang, Di Fei Shen, Qinling Yang, Ankang Li, Asish K Ghosh, Zhou Yan Bian, Ling Yan, Qi Zhu Tang, Hongliang Li, Xin Chun Yang*

*Corresponding author for this work

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Receptor-associated late transducer (RALT) is a feedback inhibitor of epidermal growth factor receptor signaling. RALT has been shown previously to be induced in the ischemic heart and to promote cardiomyocyte apoptosis in vitro. However, the role of RALT in cardiac hypertrophy remains unclear. We hypothesized that forced expression of RALT in the murine heart would protect the heart against cardiac hypertrophy in vivo. We investigated the effect of cardiac overexpression of rat RALT on cardiac hypertrophy induced by angiotensin II and isoproterenol in RALT transgenic mice and wild-type littermates. The extent of cardiac hypertrophy was assessed by 2D and M-mode echocardiography as well as by molecular and pathological analyses of cardiac samples. Constitutive expression of rat RALT in cardiac myocytes of murine heart attenuated both hypertrophic and inflammatory responses and preserved cardiac function. These beneficial effects were associated with the attenuation of the epidermal growth factor receptor-dependent cascade that was triggered by angiotensin II and isoproterenol stimulation. Additional evidence demonstrated that RALT expression blocked fibrosis in vivo and collagen synthesis in vitro. Therefore, cardiac overexpression of RALT improves cardiac function and inhibits maladaptive hypertrophy, inflammation, and fibrosis through attenuating epidermal growth factor receptor-dependent signaling.

Original languageEnglish (US)
Pages (from-to)539-548
Number of pages10
JournalHypertension
Volume53
Issue number3
DOIs
StatePublished - Mar 1 2009

Fingerprint

Transducers
Epidermal Growth Factor Receptor
Hypertrophy
Cardiomegaly
Isoproterenol
Cardiac Myocytes
Angiotensin II
Fibrosis
Transgenic Mice
Echocardiography
Collagen
Apoptosis
Inflammation

Keywords

  • Cardiac hypertrophy
  • EGFR
  • ERK1/2
  • Fibrosis
  • Heart failure
  • RALT

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Cai, Jun ; Yi, Fang Fang ; Yang, Long ; Shen, Di Fei ; Yang, Qinling ; Li, Ankang ; Ghosh, Asish K ; Bian, Zhou Yan ; Yan, Ling ; Tang, Qi Zhu ; Li, Hongliang ; Yang, Xin Chun. / Targeted expression of receptor-associated late transducer inhibits maladaptive hypertrophy via blocking epidermal growth factor receptor signaling. In: Hypertension. 2009 ; Vol. 53, No. 3. pp. 539-548.
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Targeted expression of receptor-associated late transducer inhibits maladaptive hypertrophy via blocking epidermal growth factor receptor signaling. / Cai, Jun; Yi, Fang Fang; Yang, Long; Shen, Di Fei; Yang, Qinling; Li, Ankang; Ghosh, Asish K; Bian, Zhou Yan; Yan, Ling; Tang, Qi Zhu; Li, Hongliang; Yang, Xin Chun.

In: Hypertension, Vol. 53, No. 3, 01.03.2009, p. 539-548.

Research output: Contribution to journalArticle

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AU - Cai, Jun

AU - Yi, Fang Fang

AU - Yang, Long

AU - Shen, Di Fei

AU - Yang, Qinling

AU - Li, Ankang

AU - Ghosh, Asish K

AU - Bian, Zhou Yan

AU - Yan, Ling

AU - Tang, Qi Zhu

AU - Li, Hongliang

AU - Yang, Xin Chun

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