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Abstract Details
Review: Vascular effects of PPARs in the context of NASH
Aliment Pharmacol Ther. 2022 Jun 5. doi: 10.1111/apt.17046. Online ahead of print.
1Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute & CIBEREHD, Barcelona, Spain.
2Université de Paris, Inserm, CNRS, Centre de recherche sur l'Inflammation, UMR1149, Paris, France.
3Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
4Department of Visceral Surgery and Medicine & Department for Biomedical Research, Inselspital, University of Bern, Bern, Switzerland.
5Department of Hepatology & Gastroenterology, Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum (CVK) and Campus Charité Mitte (CCM), Berlin, Germany.
6Department of Gastroenterology and Hepatology, Antwerp University Hospital, Antwerp, Belgium.
7Translational Sciences in Inflammation and Immunology, InflaMed Centre of Excellence, Laboratory of Experimental Medicine and Paediatrics, Faculty of Medicine and Health Sciences, University of Antwerp, Antwerp, Belgium.
8Université de Paris, AP-HP, Hôpital Beaujon, Service d'Hépatologie, DMU DIGEST, Centre de Référence des Maladies Vasculaires du Foie, FILFOIE, ERN RARE-LIVER, Centre de recherche sur l'inflammation, Paris, France.
Abstract
Background: Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors known to regulate glucose and fatty acid metabolism, inflammation, endothelial function and fibrosis. PPAR isoforms have been extensively studied in metabolic diseases, including type 2 diabetes and cardiovascular diseases. Recent data extend the key role of PPARs to liver diseases coursing with vascular dysfunction, including nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
Aim: This review summarises and discusses the pathobiological role of PPARs in cardiovascular diseases with a special focus on their impact and therapeutic potential in NAFLD and NASH.
Results and conclusions: PPARs may be attractive for the treatment of NASH due to their liver-specific effects but also because of their efficacy in improving cardiovascular outcomes, which may later impact liver disease. Assessment of cardiovascular disease in the context of NASH trials is, therefore, of the utmost importance, both from a safety and efficacy perspective.