Document Detail


Differential regulation of EHD3 in human and mammalian heart failure.
MedLine Citation:
PMID:  22406195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-03
Journal Detail:
Title:  Journal of molecular and cellular cardiology     Volume:  52     ISSN:  1095-8584     ISO Abbreviation:  J. Mol. Cell. Cardiol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-16     Completed Date:  2012-08-07     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  0262322     Medline TA:  J Mol Cell Cardiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1183-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA, USA.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / metabolism
Animals
Carrier Proteins / genetics,  metabolism*
Case-Control Studies
Cells, Cultured
Dogs
Gene Expression Regulation*
Heart Failure / enzymology,  metabolism*,  pathology
Heart Ventricles / enzymology,  metabolism*,  pathology
Humans
Male
Mice
Mice, Inbred C57BL
Myocytes, Cardiac / enzymology,  metabolism
NADPH Oxidase / metabolism
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species / metabolism
Sodium-Calcium Exchanger / metabolism
Grant Support
ID/Acronym/Agency:
CA105489/CA/NCI NIH HHS; CA116552/CA/NCI NIH HHS; CA87986/CA/NCI NIH HHS; CA99163/CA/NCI NIH HHS; F32 HL114252/HL/NHLBI NIH HHS; HL073986/HL/NHLBI NIH HHS; HL079031/HL/NHLBI NIH HHS; HL083422/HL/NHLBI NIH HHS; HL084583/HL/NHLBI NIH HHS; HL089836/HL/NHLBI NIH HHS; HL096805/HL/NHLBI NIH HHS; HL62494/HL/NHLBI NIH HHS; HL70250/HL/NHLBI NIH HHS; R01 CA087986/CA/NCI NIH HHS; R01 HL073986/HL/NHLBI NIH HHS; R01 HL083422/HL/NHLBI NIH HHS; R01 HL083422-07/HL/NHLBI NIH HHS; R01 HL084583/HL/NHLBI NIH HHS; R01 HL084583-07/HL/NHLBI NIH HHS; R01 HL113001/HL/NHLBI NIH HHS; UL1 TR000090/TR/NCATS NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/EHD3 protein, human; 0/Reactive Oxygen Species; 0/Sodium-Calcium Exchanger; 0/sodium-calcium exchanger 1; 11128-99-7/Angiotensin II; EC 1.6.3.1/NADPH Oxidase
Comments/Corrections

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