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DOI: 10.1055/s-0030-1269061
Extra cellular matrix remodelling in chronic cardiac allograft rejection
Objectives: Cardiac allograft vasculopathy (CAV) and fibrosis are the main representatives of chronic rejection following heart transplantation. Besides the activation of fibroblasts and vascular smooth muscle cells, remarkable changes in the cardiac extra cellular matrix (ECM) occur including the re-expression of oncofetal fibronectin or tenascin-C variants. The study was aimed to analyse the ECM remodelling in chronic rejection and to elucidate a potential role of ED-A domain containing fibronectin (ED-A+ Fn), alpha smooth muscle actin (ASMA) and B domain containing tenascin-C (B+ Tn-C).
Methods: A model of chronic rejection after heterotopic rat heart transplantation was used. Allografts, recipient and control hearts were subjected to histological assessment of rejection grade, real-time PCR based ECM gene expression analysis and to immunohistochemistry including ED-A+ Fn, ASMA and B+ Tn-C antibodies.
Results: Different histological grades of chronic rejection could be detected. Gene expression analysis revealed a relevant up-regulation of the majority of ECM genes in chronically rejected hearts. For 8 genes, there was a relevant up-regulation in allografts and corresponding recipient hearts. The grade of chronic rejection showed a clear association to the amount of ASMA positive cells. Extensive co-depositions of ED-A+ Fn, ASMA and B+ Tn-C occurred in CAV and also in fibrosis.
Conclusions: The process of chronic rejection entails an extensive ECM remodelling. ASMA is a valuable marker to detect CAV and fibrosis. There might be a functional interaction of vascular smooth muscle cells and activated fibroblasts with ED-A+ Fn and B+ Tn-C possibly contributing to the development of chronic rejection.