Fenofibrate attenuates endothelial monocyte adhesion in chronic heart failure: an in vitro study.
BACKGROUND
Inflammation is implicated in chronic heart failure (CHF). In this study, the potential inhibitory effect of peroxisome proliferator-activated receptor-alpha (PPARalpha) activator fenofibrate on monocyte adhesion in CHF patients was investigated in vitro.


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-alpha) and the inhibitory effects of fenofibrate at 25, 50, 100 and 200 microM 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-alpha-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-alpha-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-alpha-activated HAECs, probably through preventing up-regulation of cell adhesion molecules by endothelial cells in response to inflammatory stimuli. This PPARalpha activator may have the potential to ameliorate vascular inflammation in patients with CHF.
Huang
W P
WP
Division of Cardiology, Cheng-Hsin Rehabilitation Medical Centre, Taipei, Taiwan.
Yin
W H
WH
Chen
J W
JW
Jen
H L
HL
Young
M S
MS
Lin
S J
SJ
D000368:Aged; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects*; D002908:Chronic Disease; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D006333:Heart Failure / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000187:drug effects*
D019010:Vascular Cell Adhesion Molecule-1; D011345:Fenofibrate