Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension
文献类型：期刊论文
| 作者 | Zhu, Chang-Peng8; Liu, Shu-Qing8; Wang, Ke-Qi8; Xiong, Hai-Lin8; Aristu-Zabalza, Peio1; Boyer-Diaz, Zoe1; Feng, Ji-Feng8; Song, Shao-Hua6,7; Luo, Cheng5 ; Chen, Wan-Sheng4
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| 刊名 | GASTROENTEROLOGY
 |
| 出版日期 | 2024-10-01 |
| 卷号 | 167期号:5页码:993-1007 |
| 关键词 | Portal Hypertension Portal Vein Smooth Muscle Cells 5-Hydroxytryptamine HTR1A Alverine |
| DOI | 10.1053/j.gastro.2024.06.007 |
| 文献子类 | Article |
| 英文摘要 | BACKGROUND & AIMS:Portal hypertension (PH) is one of themost frequent complications of chronic liver disease. The pe-ripheral 5-hydroxytryptamine (5-HT) level was increased incirrhotic patients. We aimed to elucidate the function andmechanism of 5-HT receptor 1A (HTR1A) in the portal vein(PV) on PH.METHODS:PH models were induced by thio-acetamide injection, bile duct ligation, or partial PV ligation.HTR1A expression was detected using real-time polymerasechain reaction, in situ hybridization, and immunofluorescencestaining. In situ intraportal infusion was used to assess theeffects of 5-HT, the HTR1A agonist 8-OH-DPAT, and the HTR1Aantagonist WAY-100635 on portal pressure (PP).Htr1a-knockout (Htr1a(-/-)) rats and vascular smooth muscle cell(VSMC)-specificHtr1a-knockout (Htr1a(Delta VSMC)) mice were usedto confirm the regulatory role of HTR1A on PP.RESULTS:HTR1A expression was significantly increased in the hyper-tensive PV of PH model rats and cirrhotic patients. Additionally,8-OH-DPAT increased, but WAY-100635 decreased, the PP inrats without affecting liverfibrosis and systemic hemody-namics. Furthermore, 5-HT or 8-OH-DPAT directly induced thecontraction of isolated PVs. Genetic deletion ofHtr1ain ratsand VSMC-specificHtr1aknockout in mice prevented thedevelopment of PH. Moreover, 5-HT triggered adenosine 30,50-cyclic monophosphate pathway-mediated PV smooth musclecell contraction via HTR1A in the PV. We also confirmedalverine as an HTR1A antagonist and demonstrated its capacityto decrease PP in rats with thioacetamide-, bile duct ligation-,and partial PV ligation-induced PH.CONCLUSIONS:Ourfind-ings reveal that 5-HT promotes PH by inducing the contractionof the PV and identify HTR1A as a promising therapeutic targetfor attenuating PH. As an HTR1A antagonist, alverine is ex-pected to become a candidate for clinical PH treatment. |
| WOS关键词 | VASCULAR SMOOTH-MUSCLE ; IRRITABLE-BOWEL-SYNDROME ; LIGHT-CHAIN KINASE ; INTERNATIONAL UNION ; ALVERINE CITRATE ; SEROTONIN ; CIRRHOSIS ; PRESSURE ; MECHANISMS ; KETANSERIN |
| WOS研究方向 | Gastroenterology & Hepatology |
| 语种 | 英语 |
| WOS记录号 | WOS:001320236500001 |
| 出版者 | W B SAUNDERS CO-ELSEVIER INC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317003]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Dong, Wei-Hua; Gracia-Sancho, Jordi; Xie, Wei-Fen |
| 作者单位 | 1.IDIBAPS Hosp Clin Barcelona, CIBEREHD, Liver Vasc Biol Res Grp, Barcelona, Spain; 2.Univ Bern, Dept Biomed Res, Hepatol, Bern, Switzerland 3.Naval Med Univ, Changzheng Hosp, Dept Intervent Radiol, 415 Fengyang Rd, Shanghai, Peoples R China; 4.Naval Med Univ, Changzheng Hosp, Dept Pharm, Shanghai, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, Key Lab Receptor Res,State Key Lab Drug Res, Shanghai, Peoples R China; 6.Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Gen Surg, Shanghai, Peoples R China; 7.Naval Med Univ, Changzheng Hosp, Organ Transplantat Ctr, Shanghai, Peoples R China; 8.Naval Med Univ, Changzheng Hosp, Dept Gastroenterol, 415 Fengyang Rd, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhu, Chang-Peng,Liu, Shu-Qing,Wang, Ke-Qi,et al. Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension[J]. GASTROENTEROLOGY,2024,167(5):993-1007. |
| APA | Zhu, Chang-Peng.,Liu, Shu-Qing.,Wang, Ke-Qi.,Xiong, Hai-Lin.,Aristu-Zabalza, Peio.,...&Xie, Wei-Fen.(2024).Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension.GASTROENTEROLOGY,167(5),993-1007. |
| MLA | Zhu, Chang-Peng,et al."Targeting 5-Hydroxytryptamine Receptor 1A in the Portal Vein to Decrease Portal Hypertension".GASTROENTEROLOGY 167.5(2024):993-1007. |
入库方式： OAI收割
来源：上海药物研究所
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