Fenofibrate Modulates HO-1 and Ameliorates Endothelial Expression of Cell Adhesion Molecules in Systolic Heart Failure.
Year: 2013
Type: article
Abstract: BACKGROUND: Endothelial activation and dysfunction have been implicated in the pathogenesis and progression of heart failure (HF). In the present study, we investigated if endothelial expression of cell adhesion molecules (CAMs) is inhibited by fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist with anti-inflammatory and vascular protective effects, through the regulation of heme oxygenase-1 (HO-1). METHODS: We recruited a total of 20 patients with advanced systolic HF and 20 healthy volunteers who all provided blood samples. Cultured human pulmonary artery endothelial cells (HPAECs) were treated with 70% sera obtained from study individuals, with or without pretreatment with fenofibrate. The endothelial expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and HO-1 were analyzed by mRNA expression and Western blot. RESULTS: Stimulation of cultured HPAECs with serum from HF patients significantly activated nuclear factor-κ B (NF-κB) and increased VCAM-1 and ICAM-1 expression but attenuated HO-1 expression. Immunohistochemistry study also confirmed that CAMs were up-regulated, whereas HO-1 was down-regulated in HF patients. HO-1 small interfering RNA significantly suppressed HO-1 expression and exaggerated the HF serum-induced CAM expression, whereas HO-1 inducer cobalt protoporphyrin IX simultaneously stimulated HO-1 expression and suppressed CAM expression. Pretreatment with fenofibrate prevented the decrease of HO-1 expression and the activation of NF-κB as well as the increase of CAM expression that induced by HF patient serum. CONCLUSIONS: Our study demonstrated that fenofibrate may exert beneficial effects in patients with systolic HF through regulation of HO-1 expression and amelioration of endothelial activation. KEY WORDS: Cell adhesion molecules; Endothelial cells; Heart failure; Heme oxygenase-1; Peroxisome proliferator-activated receptor-α.
Source: Europe PMC (PubMed Central)
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2139199978