NOSTRIN is an emerging negative regulator of decompensated cirrhotic patients with portal hypertension.

IF 4 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY Digestive and Liver Disease Pub Date : 2024-09-17 DOI:10.1016/j.dld.2024.08.050
Balasubramaniyan Vairappan,Ravikumar Ts,Amit Kumar Ram,Pazhanivel Mohan,Biju Pottakkat
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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.
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NOSTRIN 是门静脉高压肝硬化失代偿期患者的一种新兴负调控因子。
背景和目的肝硬化患者体内一氧化氮(NO)生物利用率降低,导致肝内血管阻力(IHVR)增高和门静脉高压(PHT)。Nostrin是一氧化氮合成酶内皮一氧化氮合酶(eNOS)的抑制蛋白,在肝硬化伴门静脉高压时Nostrin会增加,但其确切的分子机制却鲜有记载。本研究旨在阐明 Nostrin 在肝硬化肝脏 NO 生成中的作用及相关失调。方法本研究以 60 名健康受试者和 120 名肝硬化患者为对象。结果与健康对照组相比,代偿期肝硬化患者全身 Nostrin 和 cGMP 水平升高。失代偿期肝硬化患者的 Nostrin 和 cGMP 水平进一步升高。此外,与对照组肝脏相比,肝硬化肝脏中的 Nostrin 表达明显升高,同时 eNOS 活性和肝脏 cGMP 水平降低。此外,血Nostrin浓度较高,且与疾病严重程度平行,可作为PHT肝硬化患者诊断和预后的关键生物标志物。
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来源期刊
Digestive and Liver Disease
Digestive and Liver Disease 医学-胃肠肝病学
CiteScore
6.10
自引率
2.20%
发文量
632
审稿时长
19 days
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: Original Papers Correspondence to the Editor Editorials, Reviews and Special Articles Progress Reports Image of the Month Congress Proceedings Symposia and Mini-symposia.
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