Review article: vascular effects of PPARs in the context of NASH

Aliment Pharmacol Ther. 2022 Jul;56(2):209-223. doi: 10.1111/apt.17046. Epub 2022 Jun 5.

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.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases* / metabolism
  • Diabetes Mellitus, Type 2* / metabolism
  • Humans
  • Liver
  • Non-alcoholic Fatty Liver Disease* / drug therapy
  • Peroxisome Proliferator-Activated Receptors / metabolism
  • Peroxisome Proliferator-Activated Receptors / pharmacology
  • Peroxisome Proliferator-Activated Receptors / therapeutic use

Substances

  • Peroxisome Proliferator-Activated Receptors