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-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.