Microarray analysis demonstrates up-regulation of the endothelin-1 gene with compensatory down-regulation of the ETA receptor gene in human portal vein.
Biosci Rep
; 44(7)2024 Jul 31.
Article
em En
| MEDLINE
| ID: mdl-38860875
ABSTRACT
High blood pressure in the portal vein, portal hypertension (PH), is the final common pathway in liver cirrhosis regardless of aetiology. Complications from PH are the major cause of morbidity and mortality in these patients. Current drug therapy to reduce portal pressure is mainly limited to ß-adrenergic receptor blockade but approximately 40% of patients do not respond. Our aim was to use microarray to measure the expression of â¼20,800 genes in portal vein from patients with PH undergoing transplantation for liver cirrhosis (PH, n=12) versus healthy vessels (control, n=9) to identify potential drug targets to improve therapy. Expression of 9,964 genes above background was detected in portal vein samples. Comparing PH veins versus control (adjusted P-value < 0.05, fold change > 1.5) identified 548 up-regulated genes and 1,996 down-regulated genes. The 2,544 differentially expressed genes were subjected to pathway analysis. We identified 49 significantly enriched pathways. The endothelin pathway was ranked the tenth most significant, the only vasoconstrictive pathway to be identified. ET-1 gene (EDN1) was significantly up-regulated, consistent with elevated levels of ET-1 peptide previously measured in PH and cirrhosis. ETA receptor gene (EDNRA) was significantly down-regulated, consistent with an adaptive response to increased peptide levels in the portal vein but there was no change in the ETB gene (EDNRB). The results provide further support for evaluating the efficacy of ETA receptor antagonists as a potential therapy in addition to ß-blockers in patients with PH and cirrhosis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Veia Porta
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Endotelina-1
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Receptor de Endotelina A
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Hipertensão Portal
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Cirrose Hepática
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Biosci Rep
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Reino Unido