Increased vascular endothelial growth factor mRNA in endomyocardial biopsies from allografts demonstrating severe acute rejection: A longitudinal study

• Published in: Transplant immunology Vol. 18; no. 3; pp. 264 - 274
• Main Authors: Bayliss, Julianne, Maguire, Julie A, Bailey, Michael, Leet, Angeline, Kaye, David, Richardson, Meroula, Bergin, Peter J, Dowling, John, Thomson, Napier M, Stein, Alicia N
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-01-2008
• Subjects: Acute rejection; Adult; Aged; Allergy and Immunology; Allograft vasculopathy; Biopsy; Endomyocardial biopsy; Female; Gene Expression; Graft Rejection; Heart transplantation; Heart Transplantation - immunology; Humans; Immunohistochemistry; Longitudinal Studies; Male; Middle Aged; Myocardium - immunology; Myocardium - metabolism; Myocardium - pathology; Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - metabolism; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - analysis; Vascular Endothelial Growth Factor A - genetics; Fibroblast growth factor; Endothelial cell; Interleukin-1; Platelet-derived growth factor; Tumour necrosis factor-α; RPL32; vWF; Cardiac allograft vasculopathy; ICAM-1; mRNA; ISHLT; RT-PCR; von Willebrand factor; Allograft vasculopathy; KDR; TGF-β; EB; Reverse transcription polymerase chain reaction; Vascular endothelial growth factor; EC; Acute rejection; FGF; IL-1; VEGF; Heart transplantation; IVUS; Intravascular ultrasound; Messanger RNA; AR; International Society for Heart and Lung Transplantation; TNF-α; Kinase domain receptor (VEGFR2); PDGF; Ribosomal protein L32; Transforming growth factor-β; Intercellular adhesion molecule-1; CAV; Endomyocardial biopsy; Fms-like tyrosine kinase (VEGFR1); Flt-1
• ISSN: 0966-3274; 1878-5492
• DOI: 10.1016/j.trim.2007.07.006

Abstract Investigation into the contribution of the immune system and inflammatory cascade to acute rejection (AR) and cardiac allograft vasculopathy (CAV) has implicated vascular endothelial growth factor (VEGF). The endomyocardial biopsy (EB) has proved invaluable in the diagnosis of AR, and in providing information concerning the biological processes occurring following transplantation. The association between VEGF and AR and the development of CAV was examined in endomyocardial biopsies (EBs) from a cohort of 76 heart transplant recipients. VEGF mRNA levels were quantified through real time RT-PCR in 712 EBs, obtained at routine intervals during post-operative monitoring. VEGF and leukocyte and endothelial markers were assessed in a subset of biopsies through immunohistochemistry. The results of generalised linear modelling, adjusting for covariates, revealed VEGF mRNA expression was 19% greater during severe AR as compared to no rejection ( p = 0.007). Immunohistochemical results supported these findings. Mean VEGF mRNA levels were not significant predictors for the development of CAV ( p = 0.554). However the risk of cardiac related death increased 9-fold for a 1 unit increase in mean VEGF expression ( p = 0.006). Similarly, a single unit increase in mean AR severity equated to a 10-fold increase in the risk of cardiac related death ( p < 0.005). Our data suggest that increased VEGF expression is strongly associated with severe AR and cardiac related death.