Differential regulation of EHD3 in human and mammalian heart failure

Hjalti Gudmundsson; Jerry Curran; Farshid Kashef; Jedidiah S Snyder; Sakima A Smith; Pedro Vargas-Pinto; Ingrid M Bonilla; Robert M Weiss; Mark E Anderson; Philip Binkley; Robert B Felder; Cynthia A Carnes; Hamid Band; Thomas J Hund; Peter J Mohler

doi:10.1016/j.yjmcc.2012.02.008

Back

Differential regulation of EHD3 in human and mammalian heart failure

Journal article

Peer reviewed

Differential regulation of EHD3 in human and mammalian heart failure

Hjalti Gudmundsson, Jerry Curran, Farshid Kashef, Jedidiah S Snyder, Sakima A Smith, Pedro Vargas-Pinto, Ingrid M Bonilla, Robert M Weiss, Mark E Anderson, Philip Binkley, …

Journal of molecular and cellular cardiology, Vol.52(5), pp.1183-1190

05/2012

DOI: 10.1016/j.yjmcc.2012.02.008

PMCID: PMC3360944

PMID: 22406195

Files and links (1)

url

https://www.ncbi.nlm.nih.gov/pmc/articles/3360944View

Open Access

Abstract

Electrical and structural remodeling during the progression of cardiovascular disease is associated with adverse outcomes subjecting affected patients to overt heart failure (HF) and/or sudden death. Dysfunction in integral membrane protein trafficking has long been linked with maladaptive electrical remodeling. However, little is known regarding the molecular identity or function of these intracellular targeting pathways in the heart. Eps15 homology domain-containing (EHD) gene products (EHD1–4) are polypeptides linked with endosomal trafficking, membrane protein recycling, and lipid homeostasis in a wide variety of cell types. EHD3 was recently established as a critical mediator of membrane protein trafficking in the heart. Here, we investigate the potential link between EHD3 function and heart disease. Using four different HF models including ischemic rat heart, pressure overloaded mouse heart, chronic pacing-induced canine heart, and non-ischemic failing human myocardium we provide the first evidence that EHD3 levels are consistently increased in HF. Notably, the expression of the Na/Ca exchanger (NCX1), targeted by EHD3 in heart is similarly elevated in HF. Finally, we identify a molecular pathway for EHD3 regulation in heart failure downstream of reactive oxygen species and angiotensin II signaling. Together, our new data identify EHD3 as a previously unrecognized component of the cardiac remodeling pathway. ► EHD3 is identified as a new protein associated with cardiac remodeling and disease. ► EHD3 is differentially expressed in human HF and three animal models of HF. ► Regulation of EHD3 is downstream of AngII signaling and depends on ROS formation.

Heart failure

Animal models

Regulation

Cardiac remodeling

EHD proteins

Details

Title: Subtitle: Differential regulation of EHD3 in human and mammalian heart failure
Creators: Hjalti Gudmundsson - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Jerry Curran - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Farshid Kashef - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Jedidiah S Snyder - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Sakima A Smith - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Pedro Vargas-Pinto - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Ingrid M Bonilla - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Robert M Weiss - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Mark E Anderson - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Philip Binkley - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Robert B Felder - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA
Cynthia A Carnes - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Hamid Band - Eppley Institute for Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, USA
Thomas J Hund - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Peter J Mohler - Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA
Resource Type: Journal article
Publication Details: Journal of molecular and cellular cardiology, Vol.52(5), pp.1183-1190
DOI: 10.1016/j.yjmcc.2012.02.008
PMID: 22406195
PMCID: PMC3360944
NLM abbreviation: J Mol Cell Cardiol
ISSN: 0022-2828
eISSN: 1095-8584
Publisher: Elsevier Ltd
Language: English
Date published: 05/2012
Academic Unit: Iowa Neuroscience Institute; Cardiovascular Medicine; Internal Medicine
Record Identifier: 9984065493002771

Metrics

30 Record Views

31 Times Cited - Web of Science