Comparison of PPARδ and PPARγ in inhibiting the pro-inflammatory effects of C-reactive protein in endothelial cells
Journal
International Journal of Cardiology
Journal Volume
143
Journal Issue
3
Pages
361-367
Date Issued
2010
Author(s)
Abstract
Background: Inflammation associated with endothelial cell dysfunction is a key step of atherogenesis. C-reactive protein (CRP), used to serve as a nonspecific clinical inflammation marker, has now emerged as a new marker for cardiovascular diseases. Recently, PPARδ has revealed benefits for dealing with inflammation. The relationship between CRP-induced inflammation and PPARδ agonist remains unclear. Methods: Human umbilical vein endothelial cells (HUVECs) were separated into the following groups: 25 μg CRP alone for 15 hours; CRP-treated with 1 μM PPARδ(L-165041) or 10 μM PPARγ(troglitazone) agonists, and untreated HUVECs. This research focused on the CRP underlying signaling pathways and the effects of PPAR agonists on monocyte attachment to endothelial cells. Results: Levels of interleukin-6 (IL-6) and IL-8 increased by CRP were both significantly attenuated by pretreatment with PPARδ or PPARγ agonists, but the needed dose of PPARδ to reach the same effect was less than PPARγ agonist. After incubation with CRP, immunoblotting showed a significant increase in NF-κB activation and CD32 receptor. These changes were associated with a significant increase of MCP-1 and VCAM-1 expression. PPARδ treatment not only decreased these pro-inflammatory effects in HUVECs but also significantly attenuated monocyte adhesion to endothelial cells in less dosage than PPARγ. Conclusions: The results suggest that PPARδ attenuated CRP-induced pro-inflammatory effects may through CD32 and NF-κB pathway. PPARδ may serve as a more potent therapeutic target than PPARγ in atherosclerosis or inflammatory therapy. Crown Copyright ? 2009 Published by Elsevier Ireland Ltd. All rights reserved.
Subjects
Atherosclerosis; CRP; Endothelium dysfunction; Inflammation; PPAR
SDGs
Other Subjects
4 [4 [3 (4 acetyl 3 hydroxy 2 propylphenoxy)propoxy]phenoxy]acetic acid; C reactive protein; CD32 antigen; immunoglobulin enhancer binding protein; interleukin 6; interleukin 8; monocyte chemotactic protein 1; peroxisome proliferator activated receptor delta; peroxisome proliferator activated receptor gamma; troglitazone; vascular cell adhesion molecule 1; article; atherosclerosis; cell adhesion; comparative study; controlled study; drug effect; endothelium cell; human; human cell; immunoblotting; inflammation; monocyte; priority journal; protein expression; signal transduction; umbilical vein; Atherosclerosis; C-Reactive Protein; Cell Communication; Cells, Cultured; Dose-Response Relationship, Drug; Drug Interactions; Endothelial Cells; Gene Expression; Humans; Interleukin-6; Interleukin-8; Monocytes; NF-kappa B; PPAR delta; PPAR gamma; Receptors, IgG; Umbilical Veins; Vasculitis
Type
journal article