| Category |
Medicine, Research & Experimental |
| Manuscript Type |
Basic Study |
| Article Title |
Dual therapy with vildagliptin and sacubitril/valsartan alleviates portal hypertension and inhibits soluble epoxide hydrolase in cirrhotic rats
|
| Manuscript Source |
Unsolicited Manuscript |
| All Author List |
Masafumi Oyama, Kosuke Kaji, Norihisa Nishimura, Junichi Hanatani, Tatsuya Nakatani, Naoki Nishimura, Akihiko Shibamoto, Shohei Asada, Yuki Tsuji, Koh Kitagawa, Shinya Sato, Tadashi Namisaki and Hitoshi Yoshiji |
| Funding Agency and Grant Number |
|
| Corresponding Author |
Kosuke Kaji, Associate Professor, MD, PhD, Department of Gastroenterology, Nara Medical University, Shijo-cho 840, Kashihara 634-8522, Nara, Japan. kajik@naramed-u.ac.jp |
| Key Words |
Liver sinusoidal endothelial cell; Liver fibrosis; Capillarization; Angiogenesis; Animal model |
| Core Tip |
Portal hypertension (PH) in cirrhosis is driven by increased intrahepatic resistance and loss of epoxyeicosatrienoic acids (EETs) activity due to soluble epoxide hydrolase (sEH) upregulation. While dipeptidyl peptidase-4 inhibitors (DPP4-Is) and angiotensin receptor-neprilysin inhibitors (ARNIs) may suppress sEH, their combined effect remains unclear. This study assessed the combination effect of vildagliptin and sacubitril/valsartan on PH and fibrosis in two cirrhotic rat models, choline-deficient, L-amino acid-defined, high-fat diet- and bile duct ligation-induced cirrhotic rats. Combination therapy reduced portal pressure without affecting systemic hemodynamics, improved endothelial function and sinusoidal capillarization, suppressed sEH, restored EETs, and attenuated fibrosis. These findings suggest that DPP4-I and ARNI combination therapy may represent a novel strategy for treating cirrhosis-associated PH. |
| Citation |
Oyama M, Kaji K, Nishimura N, Hanatani J, Nakatani T, Nishimura N, Shibamoto A, Asada S, Tsuji Y, Kitagawa K, Sato S, Namisaki T, Yoshiji H. Dual therapy with vildagliptin and sacubitril/valsartan alleviates portal hypertension and inhibits soluble epoxide hydrolase in cirrhotic rats. World J Gastroenterol 2025; In press |
| ISSN |
1007-9327 (print) and 2219-2840 (online) |
| Open Access |
This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/ |
| Copyright |
© The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved. |
| Permissions |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
|
| Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
| Website |
http://www.wjgnet.com |
