ArticleScientific reports2015
Statins activate the canonical hedgehog-signaling and aggravate non-cirrhotic portal hypertension, but inhibit the non-canonical hedgehog signaling and cirrhotic portal hypertension.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Novel Anti-inflammatory Treatments in Cirrhosis. A Literature-Based Study.Frontiers in medicine · 2021Pooled it
- From Pathophysiology to Practice: Evolving Pharmacological Therapies, Clinical Complications, and Pharmacogenetic Considerations in Portal Hypertension.Metabolites · 2025Review
- Sinusoidal communication in chronic liver disease.Clinical and molecular hepatology · 2025Review
- Review
- Identification of key genes for cuproptosis in carotid atherosclerosis.Frontiers in cardiovascular medicine · 2024Article
- Statin therapy: a potential adjuvant to immunotherapies in hepatocellular carcinoma.Frontiers in pharmacology · 2024Review
- Improving Management of Portal Hypertension: The Potential Benefit of Non-Etiological Therapies in Cirrhosis.Journal of clinical medicine · 2023Review
- Statin and aspirin for chemoprevention of hepatocellular carcinoma: Time to use or wait further?Clinical and molecular hepatology · 2022Review
- Statin Use in Patients With Chronic Liver Disease and Cirrhosis: Current Evidence and Future Directions.Gastroenterology research · 2022Review
- Pravastatin-induced changes in expression of long non-coding and coding RNAs in endothelial cells.Physiological reports · 2021Article
- Extrahepatic Surgery in Cirrhosis Significantly Increases Portal Pressure in Preclinical Animal Models.Frontiers in physiology · 2021Article
- Risk Factors, Pathogenesis, and Strategies for Hepatocellular Carcinoma Prevention: Emphasis on Secondary Prevention and Its Translational Challenges.Journal of clinical medicine · 2020Review
- Lifestyle and Environmental Approaches for the Primary Prevention of Hepatocellular Carcinoma.Clinics in liver disease · 2020Review
- Cirrhotic portal hypertension: From pathophysiology to novel therapeutics.World journal of gastroenterology · 2020Review
- Generic chemoprevention of hepatocellular carcinoma.Annals of the New York Academy of Sciences · 2019Review
- Rho-kinase inhibitor coupled to peptide-modified albumin carrier reduces portal pressure and increases renal perfusion in cirrhotic rats.Scientific reports · 2019Article
- Atorvastatin and Conditioned Media from Atorvastatin-Treated Human Hematopoietic Stem/Progenitor-Derived Cells Show Proangiogenic ActivityMediators of inflammation · 2019Article
- Carvedilol Ameliorates Intrahepatic Angiogenesis, Sinusoidal Remodeling and Portal Pressure in Cirrhotic Rats.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine.Journal of hepatology · 2018Review
- Hedgehog signalling in liver pathophysiology.Journal of hepatology · 2018Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
Liver cirrhosis but also portal vein obstruction cause portal hypertension (PHT) and angiogenesis. This study investigated the differences of angiogenesis in cirrhotic and non-cirrhotic PHT with special emphasis on the canonical (Shh/Gli) and non-canonical (Shh/RhoA) hedgehog pathway. Cirrhotic (bile duct ligation/BDL; CCl4 intoxication) and non-cirrhotic (partial portal vein ligation/PPVL) rats received either atorvastatin (15 mg/kg; 7d) or control chow before sacrifice. Invasive hemodynamic measurement and Matrigel implantation assessed angiogenesis in vivo. Angiogenesis in vitro was analysed using migration and tube formation assay. In liver and vessel samples from animals and humans, transcript expression was analyzed using RT-PCR and protein expression using Western blot. Atorvastatin decreased portal pressure, shunt flow and angiogenesis in cirrhosis, whereas atorvastatin increased these parameters in PPVL rats. Non-canonical Hh was upregulated in experimental and human liver cirrhosis and was blunted by atorvastatin. Moreover, atorvastatin blocked the non-canonical Hh-pathway RhoA dependently in activated hepatic steallate cells (HSCs). Interestingly, hepatic and extrahepatic Hh-pathway was enhanced in PPVL rats, which resulted in increased angiogenesis. In summary, statins caused contrary effects in cirrhotic and non-cirrhotic portal hypertension. Atorvastatin inhibited the non-canonical Hh-pathway and angiogenesis in cirrhosis. In portal vein obstruction, statins enhanced the canonical Hh-pathway and aggravated PHT and angiogenesis.
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