Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pichler, M; Rainer, PP; Schauer, S; Hoefler, G.
Cardiac fibrosis in human transplanted hearts is mainly driven by cells of intracardiac origin.
J Am Coll Cardiol. 2012; 59(11): 1008-1016.
Doi: 10.1016/j.jacc.2011.11.036
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- Führende Autor*innen der Med Uni Graz
- Pichler Martin
- Co-Autor*innen der Med Uni Graz
- Höfler Gerald
- Rainer Peter
- Schauer Silvia
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- Abstract:
- OBJECTIVES: The aim of our study was to determine the origin of collagen in the progression of myocardial fibrosis in human adult transplanted hearts. BACKGROUND: Changes in the cardiac interstitial collagen network are thought to contribute to abnormal stiffness and function of the myocardium. The origin of fibrosis-mediating fibroblasts remains incompletely understood, and conflicting data from animal models suggest that they are either derived intracardially or immigrate from extracardiac sources. METHODS: We studied endomyocardial biopsy specimens from 7 sex-mismatched (female donor heart to a male recipient) heart transplant recipients by a combination of chromogen in situ hybridization using probes specific for Y chromosomes with immunohistochemistry. On the basis of differences in genetic polymorphisms in the type III collagen gene between donor and recipient tissue, we quantitatively determined origin-specific type III collagen gene expression in fibrotic areas containing fibroblasts of putative extracardiac origin. RESULTS: In areas of increased cardiac fibrosis years after heart transplantation, a substantial number of Y chromosome-positive spindle-shaped cells with a fibroblast-like appearance were detected. Many of these cells were identified as macrophages, and measurement of origin-specific type III collagen synthesis identified cells of intracardiac origin as the main source for collagen turnover in human cardiac fibrosis. CONCLUSIONS: Our data suggest that, in human myocardium, cardiac fibrosis due to chronic allograft rejection up to 15 years after transplantation or scar formation provoked by mechanical trauma is mainly driven by fibroblasts of intracardiac origin. Antifibrotic treatment strategies, therefore, should target molecular mechanisms that induce fibrillogenesis of cells with intracardiac origin.
Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. - Find related publications in this database (using NLM MeSH Indexing)
- Adolescent -
- Adult -
- Aged -
- Collagen Type III - biosynthesis
- Female -
- Fibroblasts - metabolism
- Fibrosis -
- Graft Rejection - pathology
- Heart Injuries - pathology
- Heart Transplantation -
- Humans -
- Male -
- Middle Aged -
- Myocardium - pathology
- Find related publications in this database (Keywords)
- cardiac fibrosis
- chimerism
- fibroblasts