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Carvedilol Inhibits Angiotensin II-Induced Proliferation and Contraction in Hepatic Stellate Cells through the
Ying Wu1,2, Zhen Li3, Sining Wang1,2
1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.
Biomed Research International
|December 13, 2019
Summary
Carvedilol effectively reduces liver fibrosis by inhibiting hepatic stellate cell proliferation and contraction. It targets the angiotensin II-mediated RhoA/ROCK2 pathway, offering a potential therapeutic strategy for liver disease.
Area of Science:
- Pharmacology
- Hepatology
- Cell Biology
Background:
- Portal hypertension is often managed with beta-blockers like carvedilol.
- Hepatic stellate cells (HSCs) play a crucial role in liver fibrosis development.
- Angiotensin II (Ang II) is implicated in HSC activation and proliferation.
Purpose of the Study:
- To investigate carvedilol's effects on Ang II-induced HSC proliferation and contraction.
- To elucidate the underlying molecular mechanisms of carvedilol's action in HSCs.
- To evaluate carvedilol's efficacy in mitigating liver fibrosis in vivo.
Main Methods:
- HSC proliferation assessed by CCK-8 assay; cell cycle and apoptosis analyzed via flow cytometry.
- HSC contraction measured using collagen gel assays.
- Liver fibrosis evaluated using H&E and Sirius Red staining; protein expression analyzed by Western blot.
Main Results:
- Carvedilol dose-dependently inhibited HSC proliferation and induced G0/G1 cell cycle arrest.
- Carvedilol promoted apoptosis in Ang II-treated HSCs and inhibited Ang II-induced HSC contraction.
- Carvedilol reduced liver fibrosis markers, including collagen deposition and alpha-SMA expression, in vivo.
Conclusions:
- Carvedilol inhibits Ang II-induced HSC proliferation and contraction, thereby alleviating hepatic fibrosis.
- The mechanism involves impeding cell cycle progression and interfering with the AT1R-mediated RhoA/ROCK2 pathway.
- Carvedilol demonstrates therapeutic potential for liver fibrosis by targeting key fibrogenic pathways.
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