Document Detail


Biochemical and myofilament responses of the right ventricle to severe pulmonary hypertension.
MedLine Citation:
PMID:  21622821     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Right ventricular (RV) failure is one of the strongest predictors of mortality both in the presence of left ventricular decompensation and in the context of pulmonary vascular disease. Despite this, there is a limited understanding of the biochemical and mechanical characteristics of the pressure-overloaded RV at the level of the cardiac myocyte. To better understand this, we studied ventricular muscle obtained from neonatal calves that were subjected to hypobaric atmospheric conditions, which result in profound pulmonary hypertension. We found that RV pressure overload resulted in significant changes in the phosphorylation of key contractile proteins. Total phosphorylation of troponin I was decreased with pressure overload, predominantly reflecting changes at the putative PKA site at Ser(22/23). Similarly, both troponin T and myosin light chain 2 showed a significant decline in phosphorylation. Desmin was unchanged, and myosin-binding protein C (MyBP-C) phosphorylation was apparently increased. However, the apparent increase in MyBP-C phosphorylation was not due to phosphorylation but rather to an increase in MyBP-C total protein. Importantly, these findings were seen in all regions of the RV and were paralleled by reduced Ca(2+) sensitivity with preserved maximal Ca(2+) saturated developed force normalized to cross-sectional area in isolated skinned right ventricular myocyte fragments. No changes in total force or cooperativity were seen. Taken together, these results suggest that RV failure is mechanistically unique from left ventricular failure.
Authors:
Lori A Walker; John S Walker; Amelia Glazier; Dale R Brown; Kurt R Stenmark; Peter M Buttrick
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-05-27
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  301     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Sep 
Date Detail:
Created Date:  2011-08-31     Completed Date:  2011-11-01     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H832-40     Citation Subset:  IM    
Affiliation:
Department of Medicine, University of Colorado-Denver, Aurora, Colorado 80045, USA. lori.walker@ucdenver.edu
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MeSH Terms
Descriptor/Qualifier:
Actin Cytoskeleton / metabolism*
Animals
Animals, Newborn
Cattle
Disease Models, Animal
Excitation Contraction Coupling
Heart Ventricles / metabolism
Hemodynamics
Hyperbaric Oxygenation
Hypertension, Pulmonary / etiology,  metabolism*,  physiopathology
Muscle Proteins / metabolism*
Myocardial Contraction
Myocardium / metabolism*
Phosphorylation
Severity of Illness Index
Ventricular Dysfunction, Right / etiology,  metabolism*,  physiopathology
Ventricular Function, Right*
Ventricular Pressure
Grant Support
ID/Acronym/Agency:
1-R25-HL-103286-01/HL/NHLBI NIH HHS; HL-014985-36/HL/NHLBI NIH HHS; HL-084923-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Muscle Proteins
Comments/Corrections

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


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