Owen, NE;
Alexander, GJ;
Sen, S;
Bunclark, K;
Polwarth, G;
Pepke-Zaba, J;
Davenport, AP;
... Upton, PD; + view all
(2020)
Reduced circulating BMP10 and BMP9 and elevated endoglin are associated with disease severity, decompensation and pulmonary vascular syndromes in patients with cirrhosis.
EBioMedicine
, 56
, Article 102794. 10.1016/j.ebiom.2020.102794.
Preview |
Text
1-s2.0-S2352396420301699-main.pdf - Published Version Download (4MB) | Preview |
Abstract
BACKGROUND: BMP9, originating from the liver, and BMP10 are circulating BMPs that preserve vascular endothelial integrity. We assessed BMP9, BMP10 and soluble endoglin (sEng) levels and their relationships to liver disease severity and associated pulmonary vascular syndromes in a cohort of well-characterised liver disease patients. METHODS: Plasma samples from patients with liver disease (n = 83) and non-disease controls (n = 21) were assayed for BMP9, BMP10 and sEng. Levels were also assessed in a separate cohort of controls (n = 27) and PoPH patients (n = 8). Expression of mRNA and immunohistochemical staining was undertaken in liver biopsy specimens. Plasma BMP activity was assessed using an endothelial cell bioassay. FINDINGS: Plasma BMP9 and BMP10 levels were normal in patients with compensated cirrhosis or fibrosis without cirrhosis, but markedly reduced in patients with decompensated cirrhosis, including those with hepatopulmonary syndrome (HPS) or portopulmonary hypertension (PoPH). Liver biopsy specimens revealed reduced mRNA expression and immunostaining for these ligands. Patient plasma samples with reduced BMP9 and BMP10 levels exhibited low BMP activity that was restored with exogenous BMP9. Endoglin mRNA expression was increased in cirrhotic livers and elevated circulating sEng levels in PoPH and HPS patients suggested increased endothelial sEng shedding in these syndromes. INTERPRETATION: Plasma BMP9 and BMP10 levels are reduced in decompensated cirrhosis, leading to reduced circulating BMP activity on the vascular endothelium. The pulmonary complications of cirrhosis, PoPH and HPS, are associated with markedly reduced BMP9 and BMP10 and increased sEng levels, suggesting that supplementation with exogenous ligands might be a therapeutic approach for PoPH and HPS.
| Type: | Article |
|---|---|
| Title: | Reduced circulating BMP10 and BMP9 and elevated endoglin are associated with disease severity, decompensation and pulmonary vascular syndromes in patients with cirrhosis |
| Location: | Netherlands |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.ebiom.2020.102794 |
| Publisher version: | https://doi.org/10.1016/j.ebiom.2020.102794 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | BMP10, Bone morphogenetic protein 9, Cirrhosis, ELISA, Endoglin |
| UCL classification: | UCL 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 Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10100245 |
Archive Staff Only
 |
View Item |
