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Inflammatory cytokines, endothelial function and chronic allograft vasculopathy in children: An investigation of the donor and recipient vasculature after heart transplantation

Fenton, M; Simmonds, J; Shah, V; Brogan, P; Klein, N; Deanfield, J; Burch, M; (2016) Inflammatory cytokines, endothelial function and chronic allograft vasculopathy in children: An investigation of the donor and recipient vasculature after heart transplantation. American Journal of Transplantation , 16 (5) pp. 1159-1568. 10.1111/ajt.13643.

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Abstract

Chronic allograft vasculopathy (CAV) limits the life span of paediatric heart transplant recipients. We investigated blood markers of inflammation, endothelial dysfunction and damage to both the native and transplanted vasculature in children after heart transplantation. Serum samples were taken from pediatric heart transplant recipients for markers of inflammation and endothelial activation. The systemic vasculature was investigated using brachial artery flow-mediated dilatation and carotid artery intima-medial hyperplasia. CAV was investigated using intravascular ultrasound. Mean intima-media thickness (mIMT) > 0.5mm was used to define significant CAV. 48 children (25 male) aged 8 to 18 years were enrolled in the study. Patients were a median (IQR) 4.1(2.2 to 8.7) years after transplant. Patients had increased levels of circulating IL6 (3.86 (2.84-4.95) vs 1.66(1.22-2.63) p<0.0001*), VCAM1 (539(451-621) vs 402(342-487) p<0.001*), ICAM1 305(247-346) vs 256(224-294) p=0.002* and thrombomodulin (7.1(5.5-8.1) vs 3.57(3.03-4.71) p<0.0001*) and decreased levels of TNF alpha, E selectin and P selectin, compared with controls. The systemic vasculature was unaffected. Patients with severe CAV had raised serum von Willebrand factor and decreased serum thrombomodulin. Post-transplant thrombomodulin levels are elevated after transplant but significantly lower in those with mIMT > 0.5mm. This suggests that subclinical inflammation is present and natural anticoagulant/thrombomodulin activity is important after transplant.

Type: Article
Title: Inflammatory cytokines, endothelial function and chronic allograft vasculopathy in children: An investigation of the donor and recipient vasculature after heart transplantation
DOI: 10.1111/ajt.13643
Publisher version: http://dx.doi.org/10.1111/ajt.13643
Language: English
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science > Clinical Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/1490665
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