CHD2021 Second International Symposium on Carcinoid Heart Disease 2021 Abstracts (5 abstracts)
Enhanced expression of the proinflammatory, profibrotic molecule, vascular adhesion protein-1 in carcinoid heart disease valves
V.M. Sagar , D.A.H. Neil , B. Liu , J. Barriuso , P. Manoharan , D.A. Patten , A. Lamarca , J.W. Valle , R.P. Steeds , T. Shah , S. Shetty & C.J. Weston
Queen Elizabeth Hospital Birmingham NHS Foundation Trust and The Christie NHS Foundation Trust
Introduction Vascular adhesion protein-1 (VAP-1) is a known driver of hepatic inflammation and fibrosis, with elevated levels detected in the circulation in disease. We studied the tissue expression of VAP-1 in midgut NETs and carcinoid heart disease (CHD) alongside circulating soluble VAP-1 (sVAP-1) to determine the role of VAP-1 in NETs.
Methods Expression of VAP-1 and inflammatory and stromal markers in midgut NETs tissue, CHD valves and control valves was assessed using immunohistochemistry. sVAP-1 concentration was measured by ELISA in serum collected from two independent NET centres.
Results In midgut NETs VAP-1 protein expression was predominantly localised to fibroblast-rich areas. Tissue expression of VAP-1 was markedly increased in CHD valves (n=33) compared to control valves (n=6, aortic/mitral degenerative disease; P>0.001) and localised to neovessels and the plaque. VAP-1 expression increased with plaque maturity with myxoid regions greater than collagen and elastin rich areas. Significantly higher levels of sVAP-1 were found for midgut NETs (median 1005 ng/m;, IQR 790-1148, n=50) compared with controls (median 740 ng/ml, IQR 535-867, n=12; healthy volunteers; P=0.0014). Soluble VAP-1 levels remained high in patients with CHD (median 1280 ng/ml, IQR: 961.2-1652.0; P>0.001 vs controls, n=17). We confirmed an increase of sVAP-1 in an independent cohort (median 661 ng/ml, IQR 514-883 vs median 285 ng/ml, IQR 211-480; P>0.001), for midgut NET patients (n=40) vs controls (n= 10; benign gynaecological disease).
Conclusions VAP-1 protein expression is associated with fibrotic disease in both midgut NETs and CHD, with concomitant increases in circulating sVAP-1. These studies implicate VAP-1 in the pathophysiology of midgut NETs and CHD, with potential utility as a stratification tool and novel therapeutic target.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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