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Myocyte growth, repair, and oxidative stress following pediatric heart transplantation.
MedLine Citation:
PMID:  25118092     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cardiac remodeling is associated with plasma biomarkers of fibrinogenesis, inflammation, and oxidative stress, and upregulation of mitogenic, pro-fibrotic, and apoptotic signaling pathways. Our primary objective was to evaluate biomarker and subcellular myocardial changes in pediatric heart transplant recipients. Fifty-two-week prospective, randomized (tacrolimus, Tac, vs. cyclosporine, CsA), open-label, parallel group study. Serial myocardial biopsies were probed for mitogenic and pro-inflammatory proteins. Plasma biomarkers of oxidative stress (F2α isoprostanes, nitrotyrosine), and inflammation and oxidation (hsCRP and cystatin-C) were measured. Nine of 11 randomized patients completed the study (four Tac, five CsA). Mean levels of F2α isoprostanes, hsCRP, and cystatin-C were maximal at Week 2. Peak activation of all MAP kinases in myocardial tissue was maximal at Week 10; no association was seen with rejection. Cardiac Bax/Bcl-2 levels (index of apoptosis) correlated negatively with F2α isoprostanes at Week 2 (r = -0.88) and with hsCRP at Week 52 (r = -0.67). At Week 52, hsCRP levels correlated positively with molecular indices of cardiac cell growth. We found evidence of systemic and myocardial oxidative damage and inflammation early posttransplant, which may be related to the remodeling process. Further study is needed to better understand the cardiac and systemic repair processes following pediatric heart transplantation.
Authors:
Anne I Dipchand; Michel White; Cedric Manlhiot; Stacey Pollock-BarZiv; Tina Allain-Rooney; Lori West; Ying He; Rhian M Touyz
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-13
Journal Detail:
Title:  Pediatric transplantation     Volume:  -     ISSN:  1399-3046     ISO Abbreviation:  Pediatr Transplant     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9802574     Medline TA:  Pediatr Transplant     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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