S-Allyl-Cysteine Ameliorates Cirrhotic Portal Hypertension by Enhancing Lymphangiogenesis via a VEGF-C-Independent Manner

IF 6 2区医学 Q1 GASTROENTEROLOGY & HEPATOLOGY

Liver International Pub Date : 2025-02-18 DOI:10.1111/liv.70024

Guqing Luo, Zhenghao Wu, Qiang Fan, Chihao Zhang, Jiayun Lin, Hongjie Li, Jinbo Zhao, Haizhong Huo, Xiaoliang Qi, Guangbo Wu, Min Chen, Jiwei Yu, Lei Zheng, Meng Luo

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引用次数: 0

Abstract

Background and Aims

Lymphangiogenesis is enhanced during the development of liver cirrhosis and portal hypertension (PHT). However, hepatic lymphatic vascular system is understudied in liver cirrhosis and PHT. Hydrogen sulfide (H₂S) and related compounds have potential prolymphangiogenic effects besides its previously reported vascular-protective effects. Therefore, we aimed to investigate the effects of endogenous H₂S donor S-allyl-cysteine (SAC) on bile duct ligation (BDL)-induced liver cirrhosis and PHT.

Methods

BDL rats with cholestatic liver cirrhosis and PHT were orally administrated with SAC at 100 or 200 mg/kg/day, as well as DL-propargylglycine (PAG) or MAZ-51 injections. Hemodynamic parameters were determined, and subsequent evaluations of liver fibrosis, intrahepatic vascular resistance (IHVR) and lymphangiogensis were performed. Human lymphatic endothelial cells (hLECs) were used for in vitro verification of prolymphangiogenic effects of SAC.

Results

SAC treatment significantly decreased PP and promoted endogenous H₂S production. Liver fibrosis and IHVR were also ameliorated. Hepatic and mesenteric lymphangiogenesis were enhanced in BDL rats and further promoted by SAC despite a significant downregulation of hepatic VEGF-C. Inhibition of H₂S production by PAG significantly reduced lymphatic vessels, while inhibition of lymphangiogensis by MAZ-51 reversed the protective effects of SAC against PHT. SAC enhanced lymphangiogenic functions in vitro by promoting cellular H₂S production and activating Akt phosphorylation without altering VEGF-C/D, which were reversed by PAG and MAZ-51.

Conclusions

SAC significantly alleviated BDL-induced liver cirrhosis and PHT. Meanwhile, elevated H₂S induced by SAC facilitated lymphangiogenesis via a VEGF-C-independent manner, which contributed to the alleviation of PHT.

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来源期刊

Liver International 医学-胃肠肝病学

CiteScore

13.90

自引率

4.50%

发文量

348

审稿时长

2 months

期刊介绍： Liver International promotes all aspects of the science of hepatology from basic research to applied clinical studies. Providing an international forum for the publication of high-quality original research in hepatology, it is an essential resource for everyone working on normal and abnormal structure and function in the liver and its constituent cells, including clinicians and basic scientists involved in the multi-disciplinary field of hepatology. The journal welcomes articles from all fields of hepatology, which may be published as original articles, brief definitive reports, reviews, mini-reviews, images in hepatology and letters to the Editor.