Expression patterns of vascular endothelial growth factor in human cardiac allografts: association with rejection.
BACKGROUND
Vascular endothelial growth factor (VEGF), a major angiogenesis factor, has been found to have proinflammatory properties in vivo in several chronic inflammatory diseases. However, little is known of the expression or function of VEGF in acute and chronic allograft rejection.


METHODS
In a cross-sectional analysis, we evaluated the expression of VEGF by immunohistochemistry in human endomyocardial biopsies (n=101) from 10 cardiac transplant patients. We correlated expression (scores from 0-4) with CD3+ T cell, CD68+ monocyte and macrophage infiltrates, or rejection (International Society of Heart and Lung Transplantation grades 0-4). In addition, we evaluated the temporal patterns of VEGF expression in consecutive biopsies from seven patients (total of 74 biopsies) who were assessed for the development of graft vascular disease (GVD) by intravascular ultrasonography at 1 year posttransplantation.


RESULTS
VEGF is expressed in normal human endomyocardial biopsies at low levels and is induced (scores >1) in association with CD3+ T cells (odds ratio [OR], 19.90; P<0.001), CD68+ monocyte and macrophage infiltrates (OR, 8.49; P<0.001), and all grades of acute rejection (OR, 5.4; P<0.001). Increases in VEGF expression were persistent during the first posttransplant year in biopsies from four patients who demonstrated evidence of GVD (mean annual score of 2.3). In contrast, limited expression of VEGF was found in three patients without GVD (mean annual score 1.2).


CONCLUSIONS
These findings define VEGF as an important proinflammatory cytokine after transplantation and indicate that its expression pattern might identify patients at risk for the development of GVD.
Reinders
Marlies E J
ME
Department of Medicine, and Department of Pediatrics Children's Hospital, Boston, Massachusetts 02115, USA.
Fang
James C
JC
Wong
William
W
Ganz
Peter
P
Briscoe
David M
DM
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D016228:Endothelial Growth Factors / Q000032:analysis* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D006087:Graft vs Host Reaction / Q000276:immunology; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000032:analysis* / Q000378:metabolism; D008222:Lymphokines / Q000032:analysis* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D020033:Protein Isoforms / Q000235:genetics; D013997:Time Factors; D014184:Transplantation, Homologous; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D015415:Biomarkers; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors