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.
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