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Recipient-derived neoangiogenesis of arterioles and lymphatics in quilty lesions of cardiac allografts.

Jonigk D, Lehmann U, Stuht S, Wilhelmi M, Haverich A, Kreipe H, Mengel M

Institute of Pathology, Medizinische Hochschule Hannover, Germany.

BACKGROUND: The contribution of extracardiac cells to tissue turnover in heart allografts has recently been demonstrated. Complex subendocardial infiltrates, known as Quilty lesions, are frequently observed in cardiac allografts. The origin of the different cellular components of Quilty lesions is not known. METHODS: Different constituents of these lymphonodular infiltrates were analyzed with regard to donor or recipient derivation. Laser-assisted microdissection with subsequent short tandem repeat polymerase chain reaction (PCR)-based "genetic fingerprinting" was employed. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for confirmation in cases of gender-mismatched transplantation. Expression of angiogenic factors (FGF-2, PDGF-alpha, PDGF-alpha-receptor, and VEGF-alpha) was analyzed by quantitative real-time reverse-transcription PCR and immunohistochemistry. RESULTS: The inflammatory, nonvascular component of Quilty lesions was completely recipient-derived. Blood vessels were of mixed origin. Different compartments of blood vessels displayed different rates of recipient derivation (endothelium up to 50%, smooth muscle cells up to 15%). Lymphatic vessels were mainly recipient-derived. Of the angiogenic molecules, VEGF-alpha expression was significantly increased in the adjacent myocardium, compared to controls and the Quilty lesions themselves. CONCLUSIONS: The inflammatory compartment of Quilty lesions is of recipient origin and shows chimeric neoangiogenesis of blood and lymphatic vessels. VEGF-alpha produced in the adjacent myocardium appears to stimulate the chimeric neoangiogenesis.

Published 30 November 2007 in Transplantation, 84(10): 1335-42.
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