title: Chronic cardiac allograft rejection: critical role of ED-A(+)  fibronectin and implications for targeted therapy strategies.
abstract: Chronic cardiac allograft rejection is characterized by cardiac allograft vasculopathy (CAV) and cardiac interstitial fibrosis (CIF) causing severe long-term complications after heart transplantation and determining allograft function and patients' prognosis. Until now, there have been no sufficient preventive or therapeutic strategies. CAV and CIF are accompanied by changes in the extracellular matrix, including re-expression of the fetal fibronectin splice variant known as ED-A(+) fibronectin. This molecule has been shown to be crucial for the development of myofibroblasts (MyoFbs) as the main cell type in CIF and for the activation of vascular smooth muscle cells (VSMCs) as the main cell type in CAV. Relevant re-expression and protein deposition of ED-A(+) fibronectin has been demonstrated in animal models of chronic rejection, with spatial association to CAV and CIF, and a quantitative correlation to the rejection grade. The paper by Booth et al published in this issue of The Journal of Pathology could prove for the first time the functional importance of ED-A(+) fibronectin for the development of CIF as a main component of chronic cardiac rejection. Thus, promising conclusions for the development of new diagnostic, preventive, and therapeutic strategies for chronic cardiac rejection focusing on ED-A(+) fibronectin can be suggested.
authors.affiliation: Department of Internal Medicine I, University Hospital Jena, Erlanger Allee 101, 07740 Jena, Germany. marcus.franz@med.uni-jena.de
authors.forename: Marcus
authors.initials: M
authors.lastname: Franz
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Alexander
authors.initials: A
authors.lastname: Berndt
mesh_terms: D000818:Animals; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D005355:Fibrosis / Q000473:pathology*; D006084:Graft Rejection / Q000473:pathology*; D016027:Heart Transplantation / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*
chemical_list: D005353:Fibronectins