title: Inflammatory Cytokines, Endothelial Function, and Chronic Allograft Vasculopathy in Children: An Investigation of the Donor and Recipient Vasculature After Heart Transplantation.
abstract: Chronic allograft vasculopathy (CAV) limits the lifespan of pediatric 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) > 0.5 mm was used to define significant CAV. Forty-eight children (25 male) aged 8-18 years were enrolled in the study. Patients were a median (interquartile range) 4.1 (2.2-8.7) 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), vascular cell adhesion molecule 1 (539 [451-621] vs. 402 [342-487] p < 0.001), intracellular adhesion molecule 1 305 (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 tumor necrosis factor-α, 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. Posttransplant thrombomodulin levels are elevated after transplant but significantly lower in those with mIMT > 0.5 mm. This suggests that subclinical inflammation is present and that natural anticoagulant/thrombomodulin activity is important after transplant.
authors.affiliation: Department of Cardiothoracic Transplant, Great Ormond Street Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Fenton
authors.affiliation: Department of Cardiothoracic Transplant, Great Ormond Street Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Simmonds
authors.affiliation: UCL Institute of Child Health, Great Ormond Street Hospital, London, UK.
authors.forename: V
authors.initials: V
authors.lastname: Shah
authors.affiliation: UCL Institute of Child Health, Great Ormond Street Hospital, London, UK.
authors.forename: P
authors.initials: P
authors.lastname: Brogan
authors.affiliation: UCL Institute of Child Health, Great Ormond Street Hospital, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Klein
authors.affiliation: UCL Institute of Cardiovascular Sciences, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Deanfield
authors.affiliation: Department of Cardiothoracic Transplant, Great Ormond Street Hospital, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Burch
mesh_terms: D000293:Adolescent; D064591:Allografts; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000150:complications / Q000601:surgery; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D014652:Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators