Document Detail


Myocyte cytoskeletal disorganization and right heart failure in hypoxia-induced neonatal pulmonary hypertension.
MedLine Citation:
PMID:  10993804     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have demonstrated that environmentally or genetically induced changes in the intracellular proteins that compose the cytoskeleton can contribute to heart failure. Because neonatal right ventricular myocytes are immature and are in the process of significant cytoskeletal change, we hypothesized that they may be particularly susceptible to pressure stress. Newborn calves exposed to hypobaric hypoxia (barometric pressure = 430 mmHg) for 14 days developed severe pulmonary hypertension (pulmonary arterial pressure = 101 +/- 6 vs. 27 +/- 1 mmHg) and right heart failure compared with age-matched controls. Light microscopy showed partial loss of myocardial striations in the failing neonatal right but not left ventricles and in neither ventricle of adolescent cattle dying of altitude-induced right heart failure. In neonatal calves, immunohistochemical analysis of the cytoskeletal proteins (vinculin, metavinculin, desmin, vimentin, and cadherin) showed selectively, within the failing right ventricles, patchy areas characterized by loss and disorganization of costameres and intercalated discs. Within myocytes from the failing ventricles, vinculin and desmin were observed to redistribute diffusely within the cytosol, metavinculin appeared in disorganized clumps, and vimentin immunoreactivity was markedly decreased. Western blot analysis of the failing right ventricular myocardium showed, compared with control, vinculin and desmin to be little changed in total content but redistributed from insoluble (structural) to soluble (cytosolic) fractions; metavinculin total content was markedly decreased, tubulin content increased, particularly in the structural fraction, and cadherin total content and distribution were unchanged. We conclude that hypoxic pulmonary hypertensive-induced neonatal right ventricular failure is associated with disorganization of the cytoskeletal architecture.
Authors:
M S Lemler; R D Bies; M G Frid; A Sastravaha; L S Zisman; T Bohlmeyer; A M Gerdes; J T Reeves; K R Stenmark
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  279     ISSN:  0363-6135     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2000 Sep 
Date Detail:
Created Date:  2000-10-12     Completed Date:  2000-10-12     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H1365-76     Citation Subset:  IM    
Affiliation:
Division of Cardiology, Department of Pediatrics, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Newborn
Anoxia / complications*
Cadherins / metabolism
Cattle
Cytoskeleton / ultrastructure*
Echocardiography
Fluorescent Antibody Technique
Heart Failure / etiology,  pathology*,  ultrasonography
Heart Ventricles / metabolism,  pathology
Hemodynamics
Hypertension, Pulmonary / complications*
Immunohistochemistry
Intermediate Filament Proteins / metabolism
Male
Muscle Proteins / metabolism
Myocardium / metabolism,  pathology*
Organ Size
Grant Support
ID/Acronym/Agency:
HL-14985/HL/NHLBI NIH HHS; HL-46481/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cadherins; 0/Intermediate Filament Proteins; 0/Muscle Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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