Biomarkers for Cardiac Allograft Vasculopathy

Eisenga, M.F. (Michele-Freerk) (2013) Biomarkers for Cardiac Allograft Vasculopathy. thesis, Medicine.

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Abstract

Background: Cardiac allograft vasculopathy(CAV) is the most important cause of late death after heart transplantation. It causes diffuse accelerated intimal hyperplasia in the coronary arteries of the transplanted heart which can lead to ischemia. Endothelial damage seems to be the central event in the pathogenesis of CAV. Factors that are associated with endothelial injury and repair could function as sensitive biomarkers for the detection of CAV. Methods: In a cross-sectional cohort study different circulating protein markers of endothelial injury and repair were measured. We measured 15 angiogenesis-related proteins using enzyme-linked immunosorbent assay or a Luminex based multi-analyte profiling technique in serum and plasma of 48 pediatric heart transplant recipients. Sixteen patients had angiographically present CAV (1 patient grade IV CAV, 6 patients grade III CAV and 10 patients with grade II CAV) and 29 age- and gender-matched controls did not have CAV. Results: The study population was 54% male with a mean age of 7 ± 1 year. We found that three candidate biomarkers, vascular endothelial growth factor(VEGF)-A, thrombospondin-2(TSP-2) and angiogenin showed statistical trends with established CAV (p<0.1). Multivariate analysis showed highly significant values for VEGF-A and TSP-2. Furthermore, receiver-operating characteristic curve analysis showed that the combination VEGF-A by Luminex or VEGF-A by Elisa in combination with TSP-2 has good performance characteristics for the diagnosis of CAV. (AUC=0.764 VEGF-A Luminex + TSP-2; p=0.032, AUC =0.871 VEGF-A Elisa + TSP-2; p=0.004) Conclusions: Elevated plasma levels of VEGF-A and TSP-2 demonstrate strong correlation with established CAV. These angiogenesis-related proteins may serve as clinically, reliable biomarkers for CAV in the future.

Item Type:	Thesis (Thesis)
Supervisor name:	Son, Prof. W.J. Van and Department of Nephrology and University Medical center Groningen
Faculty:	Medical Sciences
Date Deposited:	25 Jun 2020 10:47
Last Modified:	25 Jun 2020 10:47
URI:	https://umcg.studenttheses.ub.rug.nl/id/eprint/828

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