{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T14:15:29Z","timestamp":1779286529886,"version":"3.51.4"},"reference-count":44,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>\n                      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 (H\n                      <jats:sub>2<\/jats:sub>\n                      S) and related compounds have potential prolymphangiogenic effects besides its previously reported vascular\u2010protective effects. Therefore, we aimed to investigate the effects of endogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S donor S\u2010allyl\u2010cysteine (SAC) on bile duct ligation (BDL)\u2010induced liver cirrhosis and PHT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>BDL rats with cholestatic liver cirrhosis and PHT were orally administrated with SAC at 100 or 200\u2009mg\/kg\/day, as well as DL\u2010propargylglycine (PAG) or MAZ\u201051 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\u00a0vitro verification of prolymphangiogenic effects of SAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      SAC treatment significantly decreased PP and promoted endogenous H\n                      <jats:sub>2<\/jats:sub>\n                      S 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\u2010C. Inhibition of H\n                      <jats:sub>2<\/jats:sub>\n                      S production by PAG significantly reduced lymphatic vessels, while inhibition of lymphangiogensis by MAZ\u201051 reversed the protective effects of SAC against PHT. SAC enhanced lymphangiogenic functions in\u00a0vitro by promoting cellular H\n                      <jats:sub>2<\/jats:sub>\n                      S production and activating Akt phosphorylation without altering VEGF\u2010C\/D, which were reversed by PAG and MAZ\u201051.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      SAC significantly alleviated BDL\u2010induced liver cirrhosis and PHT. Meanwhile, elevated H\n                      <jats:sub>2<\/jats:sub>\n                      S induced by SAC facilitated lymphangiogenesis via a VEGF\u2010C\u2010independent manner, which contributed to the alleviation of PHT.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70024","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T02:36:32Z","timestamp":1739932592000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["S\u2010Allyl\u2010Cysteine Ameliorates Cirrhotic Portal Hypertension by Enhancing Lymphangiogenesis via a\n                    <scp>VEGF<\/scp>\n                    \u2010C\u2010Independent Manner"],"prefix":"10.1111","volume":"45","author":[{"given":"Guqing","family":"Luo","sequence":"first","affiliation":[{"name":"Department of General Surgery Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University  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