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Differential regulation of EHD3 in human and mammalian heart failure

Hjalti Gudmundsson1, Jerry Curran, Farshid Kashef

  • 1Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.

Journal of Molecular and Cellular Cardiology
|March 13, 2012
PubMed

Insights

Eps15 homology domain-containing protein 3 (EHD3) is elevated in heart failure (HF) and contributes to cardiac remodeling. This study identifies EHD3 as a novel factor in HF progression, linked to reactive oxygen species and angiotensin II signaling.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cellular Biology

Background:

  • Cardiovascular disease progression involves electrical and structural remodeling, leading to heart failure (HF) and sudden death.
  • Integral membrane protein trafficking dysfunction is linked to maladaptive electrical remodeling in the heart.
  • The molecular pathways governing intracellular targeting in the heart remain largely unknown.

Purpose of the Study:

  • To investigate the role of Eps15 homology domain-containing protein 3 (EHD3) in heart disease.
  • To determine if EHD3 levels change during heart failure.
  • To elucidate the regulatory pathways of EHD3 in the context of cardiac remodeling.

Main Methods:

  • Analysis of EHD3 expression in four distinct heart failure models: ischemic rat heart, pressure-overloaded mouse heart, pacing-induced canine heart, and human failing myocardium.
  • Assessment of Na/Ca exchanger 1 (NCX1) expression in relation to EHD3.
  • Investigation of EHD3 regulation by reactive oxygen species and angiotensin II signaling.

Main Results:

  • EHD3 levels were consistently increased across all four investigated heart failure models.
  • Expression of the EHD3-targeted Na/Ca exchanger (NCX1) was also elevated in heart failure.
  • A molecular pathway for EHD3 regulation in heart failure was identified, involving downstream effects of reactive oxygen species and angiotensin II.

Conclusions:

  • EHD3 is a previously unrecognized component of the cardiac remodeling pathway in heart failure.
  • Increased EHD3 expression is a consistent finding in various forms of heart failure.
  • EHD3 function in the heart is regulated by signaling pathways implicated in heart failure progression.

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