Linked Life Data

12479237

Source:http://linkedlifedata.com/resource/pubmed/id/12479237

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-12-13
pubmed:abstractText
Excitation-contraction coupling and intracellular Ca2+ homeostasis are altered in heart failure. We tested the hypothesis that these changes are related to disturbed Ca2+ handling of the sarcoplasmic reticulum (SR). Isolated, electrically stimulated trabeculae were obtained from end-stage failing (NYHA IV) and nonfailing human hearts. Isometric twitch tension, intracellular Ca2+ transients (aequorin method) and SR Ca2+ content (rapid cooling contractures) were assessed under basal conditions (1 Hz, 37 degrees C) as well as after stepwise increasing rest intervals from 2-240 s (post-rest contractions). Protein expression of SERCA2a and phospholamban (Western blot) was assessed in a subset of failing trabeculae. In addition, the effects of SERCA1 overexpression on contractile function of isolated myocytes was tested. On average, post-rest twitch tension continuously increased with increasing rest intervals in nonfailing, but declined with rest intervals longer than 15 s in failing myocardium. The rest-dependent contractile changes were accompanied by parallel changes in intracellular Ca2+ transients. Failing trabeculae (n = 40) were grouped (group A: post-rest potentiation (force of contraction > pre-rest twitch force) after 120 s rest interval; group B: post-rest decay (force of contraction < pre-rest twitch force) after 120 s rest interval), and post-rest contractile function was related to SERCA2a and PLB expression. While PLB protein expression was not different, SERCA2a protein expression as well as SERCA2a/PLB ratio was significantly higher in group A vs. group B. Transfection of SERCA1 increased shortening amplitude and enhanced relaxation kinetics in failing human myocytes. In conclusion, SR Ca2+ handling is severely altered in human heart failure. Reduced SR Ca2+ release is due to diminished SR Ca2+ content directly related to a depressed expression of SERCA2a protein. Enhancing SERCA function or expression may improve SR Ca2+ handling in failing human myocardium.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0300-8428
pubmed:author
pubmed:issnType
Print
pubmed:volume
97 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
I63-71
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Sarcoplasmic reticulum Ca2+ load in human heart failure.
pubmed:affiliation
Labor für Molekulare Kardiologie und Herzmuskelphysiologie, Abteilung Kardiologie und Angiologie, Georg-August-Universität Göttingen, Robert-Koch-Str. 40, 37085 Göttingen, Germany. pieske@med.uni-goettingen.de
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't