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- Title
Fenofibrate attenuates endothelial monocyte adhesion in chronic heart failure: an in vitro study.
- Authors
Huang, W. P.; Yin, W. H.; Chen, J. W.; Jen, H. L.; Young, M. S.; Lin, S. J.
- Abstract
Background Inflammation is implicated in chronic heart failure (CHF). In this study, the potential inhibitory effect of peroxisome proliferator-activated receptor-α (PPARα) activator fenofibrate on monocyte adhesion in CHF patients was investigated in vitro. Materials and methods Isolated peripheral blood mononuclear cells (PBMCs) were collected from 36 patients (aged 65 ± 8 years) with symptomatic CHF and from 12 healthy control subjects. The cultured human aortic endothelial cells (HAECs) were stimulated with or without 2 ng mL−1 tumour necrosis factor-alpha (TNF-α) and the inhibitory effects of fenofibrate at 25, 50, 100 and 200 μM on endothelial mononuclear cell adhesion were tested. Furthermore, the HAECs were stimulated with 70% sera obtained from CHF patients and control individuals, respectively, with or without pretreatments with fenofibrate. The endothelial expression of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) was then confirmed by mRNA expression and Western blot. Results We found that the increased adhesion of PBMCs to TNF-α-stimulated HAECs in CHF patients was reduced when the HAECs were pretreated with fenofibrate (31% inhibition, P = 0·0121). However, pretreatment of the isolated PBMCs collected from CHF patients with fenofibrate failed to suppress their adherence to TNF-α-stimulated HAECs. Furthermore, stimulation of cultured HAECs with CHF patient sera significantly increased VCAM-1 and ICAM-1 expression, which could also be inhibited by fenofibrate. Conclusions The fenofibrate directly inhibits monocyte binding by TNF-α-activated HAECs, probably through preventing up-regulation of cell adhesion molecules by endothelial cells in response to inflammatory stimuli. This PPARα activator may have the potential to ameliorate vascular inflammation in patients with CHF.
- Subjects
FENOFIBRATE; MONOCYTES; CELL adhesion molecules; CELL communication; HEART failure
- Publication
European Journal of Clinical Investigation, 2009, Vol 39, Issue 9, p775
- ISSN
0014-2972
- Publication type
Article
- DOI
10.1111/j.1365-2362.2009.02176.x