{"title":"NOSTRIN is an emerging negative regulator of decompensated cirrhotic patients with portal hypertension.","authors":"Balasubramaniyan Vairappan,Ravikumar Ts,Amit Kumar Ram,Pazhanivel Mohan,Biju Pottakkat","doi":"10.1016/j.dld.2024.08.050","DOIUrl":null,"url":null,"abstract":"BACKGROUND AND AIMS\r\nDecreased nitric oxide (NO) bioavailability in a cirrhotic liver contributes to high intrahepatic vascular resistance (IHVR) and portal hypertension (PHT). Nostrin is an inhibitory protein of NO synthesising enzyme endothelial NO synthase (eNOS), shown to increase in cirrhosis with PHT, however, the precise molecular mechanism is poorly documented. This study aimed to elucidate the role of Nostrin and associated derangement in hepatic NO generation in cirrhotic liver. Further, we investigate whether Nostrin could be a biomarker in the progression of cirrhosis.\r\n\r\nMETHODS\r\nThis study was conducted on sixty healthy subjects and 120 cirrhotic patients. In addition, liver tissue samples were collected from cirrhotic patients for the analysis of Nostrin, eNOS and inflammatory markers.\r\n\r\nRESULTS\r\nWhen compared to healthy controls, systemic levels of Nostrin and cGMP were elevated in compensated cirrhosis. In decompensated cirrhosis, further robust increases in Nostrin and cGMP were noted. Furthermore, Nostrin expression was considerably higher whilst reduced eNOS activity and hepatic cGMP levels in cirrhotic liver compared to control liver.\r\n\r\nCONCLUSIONS\r\nIn cirrhotic patients, a robust increase in hepatic Nostrin expression may reduce eNOS activity and associated local NO generation. Furthermore, Blood Nostrin concentration was higher and parallel to disease severity and could be a key diagnostic and prognostic biomarker in cirrhotic patients with PHT.","PeriodicalId":11268,"journal":{"name":"Digestive and Liver Disease","volume":"6 1","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Digestive and Liver Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.dld.2024.08.050","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
BACKGROUND AND AIMS
Decreased nitric oxide (NO) bioavailability in a cirrhotic liver contributes to high intrahepatic vascular resistance (IHVR) and portal hypertension (PHT). Nostrin is an inhibitory protein of NO synthesising enzyme endothelial NO synthase (eNOS), shown to increase in cirrhosis with PHT, however, the precise molecular mechanism is poorly documented. This study aimed to elucidate the role of Nostrin and associated derangement in hepatic NO generation in cirrhotic liver. Further, we investigate whether Nostrin could be a biomarker in the progression of cirrhosis.
METHODS
This study was conducted on sixty healthy subjects and 120 cirrhotic patients. In addition, liver tissue samples were collected from cirrhotic patients for the analysis of Nostrin, eNOS and inflammatory markers.
RESULTS
When compared to healthy controls, systemic levels of Nostrin and cGMP were elevated in compensated cirrhosis. In decompensated cirrhosis, further robust increases in Nostrin and cGMP were noted. Furthermore, Nostrin expression was considerably higher whilst reduced eNOS activity and hepatic cGMP levels in cirrhotic liver compared to control liver.
CONCLUSIONS
In cirrhotic patients, a robust increase in hepatic Nostrin expression may reduce eNOS activity and associated local NO generation. Furthermore, Blood Nostrin concentration was higher and parallel to disease severity and could be a key diagnostic and prognostic biomarker in cirrhotic patients with PHT.
期刊介绍:
Digestive and Liver Disease is an international journal of Gastroenterology and Hepatology. It is the official journal of Italian Association for the Study of the Liver (AISF); Italian Association for the Study of the Pancreas (AISP); Italian Association for Digestive Endoscopy (SIED); Italian Association for Hospital Gastroenterologists and Digestive Endoscopists (AIGO); Italian Society of Gastroenterology (SIGE); Italian Society of Pediatric Gastroenterology and Hepatology (SIGENP) and Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD).
Digestive and Liver Disease publishes papers on basic and clinical research in the field of gastroenterology and hepatology.
Contributions consist of:
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Correspondence to the Editor
Editorials, Reviews and Special Articles
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