Document Detail


S100A1 gene transfer in myocardium.
MedLine Citation:
PMID:  17107875     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
S100A1, a Ca superset2+-binding protein of the EF-hand type, is preferentially expressed in myocardial tissue and has been shown to enhance cardiac contractile performance by regulating both sarcoplasmic reticulum (SR) Ca superset2+-handling and myofibrillar Ca superset2+-responsiveness. In cardiac disease, the expression of S100A1 is dynamically altered as it is significantly down-regulated in end stage human heart failure (HF), and it is up-regulated in compensated hypertrophy. Therefore, the delivery of a transgene encoding for S100A1 to the myocardium might be an attractive strategy for improving cardiac function in HF by replacing lost endogenous S100A1. In this study we sought to test whether exogenous S100A1 gene delivery to alter global cardiac function is feasible in the normal rabbit heart. An adenoviral S100A1 transgene (AdvS100A1) also containing the green fluorescent protein (GFP) was delivered using an intracoronary injection method with a dose of 5 x 10 superset11 total virus particles (tvp) (n = 8). Rabbits treated with either a GFP-only adenovirus (AdvGFP) or saline were used as control groups (n = 11 each). Seven days after global myocardial in vivo gene delivery hemodynamic parameters were assessed. S100A1 overexpression as a result of the intracoronary delivery of AdvS100A1 significantly increased left ventricular (LV) +dP/dt subsetmax, -dP/dt subsetmin and systolic ejection pressure (SEP) compared to both control groups after administration of isoproterenol (0.1, 0.5 and 1.0 microg/kgBW/min), while contractile parameters remained unchanged under basal conditions. These results demonstrate that global myocardial in vivo gene delivery is possible and that myocardial S100A1 overexpression can increase cardiac performance. Therefore, substitution of down-regulated S100A1 protein expression levels may represent a potential therapeutic strategy for improving the cardiac performance of the failing heart.
Authors:
S T Pleger; P Most; B Heidt; M Voelkers; J A Hata; H A Katus; A Remppis; W J Koch
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of medical research     Volume:  11     ISSN:  0949-2321     ISO Abbreviation:  Eur. J. Med. Res.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-11-19     Completed Date:  2007-01-30     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  9517857     Medline TA:  Eur J Med Res     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  418-22     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine III, Division of Cardiology, University of Heidelberg, Otto-Meyerhof-Zentrum, Im Neuenheimer Feld 350, 69120 Heidelberg, Germany. sven.pleger@jefferson.edu
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae
Animals
Gene Transfer Techniques*
Genetic Vectors
Green Fluorescent Proteins
Injections
Male
Myocardial Contraction / genetics*
Myocardium / metabolism*
Rabbits
S100 Proteins / genetics*,  metabolism
Ventricular Function, Left
Grant Support
ID/Acronym/Agency:
R01 HL56205/HL/NHLBI NIH HHS; R01 HL59533/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/S100 Proteins; 0/S100A1 protein; 147336-22-9/Green Fluorescent Proteins

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