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

Abstract

Summary 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.

C Allele of the PPARδ+294T>C Polymorphism Confers a Higher Risk of Hypercholesterolemia, but not Obesity and Insulin Resistance: A Systematic Review and Meta-Analysis

“…Peroxisome proliferator activated receptors (PPARs) are ligand-activated transcriptional factors, which belong to the nuclear receptor superfamily and play key roles in lipid and glucose metabolism [1][2][3][4]. Humans have three subtypes of PPARs: PPARα, PPARδ (also named as PPARβ), and PPARγ.…”

NASH drug treatment development: challenges and lessons

“…[105][106][107] Recent data extend the key role of PPARs to liver diseases occurring with vascular dysfunction, including NAFLD. 108 PPAR-gamma is expressed in many tissues but its splicing isoform (PPAR-gamma2) is expressed solely in adipocytes and PPARgamma activation increases the production of adiponectin from adipocytes 109 that is an adipokine protein with insulin-sensitizing and anti-inflammatory effects.…”

The metabolic evaluation of pemafibrate in nonalcoholic fatty liver disease‐related cardiovascular diseases

“…Notably, Guixé-Muntet et al showed that the pharmacotherapy by targeting specific PPARs through modulating vascular effects provides novel insights into the treatment of nonalcoholic steatohepatitis-related CVD, including endothelial dysfunction, coagulation, inflammation, and vascular remodeling. 5 In addition, further research into the assessment of NAFLD-related CVD using a panel of PPAR-targeted biomarkers is possible, such as apolipoprotein B, interleukins 8 and 10, sterol regulatory element binding protein-1c, and tumor necrosis factor-alpha. 6 Thus, the investigation of pemafibrate in alleviating NAFLD-related CVD through specific biomarkers should be considered.…”