Eicosapentaenoic Acid Inhibits Mitogen-Induced Endothelin-1 Production and DNA Synthesis in Cultured Bovine Mesangial Cells

Abstract

The present study was designed to examine whether eicosapentaenoic acid (EPA) inhibits the production of basal or stimulated endothelin (ET)-1 by platelet-derived growth factor (PDGF)-BB or epidermal growth factor (EGF), and DNA synthesis in cultured bovine mesangial cells. PDGF-BB and EGF stimulated ET-1 secretion in a dose-dependent fashion in these cells. EPA (10–100 µM) exhibited dose-related inhibition of PDGF-BB- and EGF-stimulated ET-1 secretion. EPA had no inhibitory effects on basal ET-1 secretion in these cells. Moreover, 50 µM EPA significantly attenuated PDGF-BB- and EGF-stimulated [³H]thymidine incorporation into mesangial cells. Receptor-binding experiments showed that EPA competitively inhibited ¹²⁵I-PDGF-BB or ¹²⁵I-EGF binding to mesangial cell surface receptors. Scatchard analysis for PDGF-BB receptor or EGF receptor revealed a linear regression fit and one binding site. Pretreatment with 50 µM EPA suppressed the number of maximum binding sites, but did not affect the K_d values. These results indicate that EPA potentially inhibits mesangial cell ET-1 production, when stimulated by PDGF-BB or EGF. This inhibitory effect of EPA could be related to the attenuation of mesangial cell proliferation via inhibition of the binding of PDGF-BB or EGF to their receptors due to alteration of the physicochemical characteristics of the cell membrane.

Eicosapentaenoic acid inhibits PDGF‐induced mitogenesis and cyclin D1 expression via TGF‐β in mesangial cells

“…In previous studies by Nitta et al (1998) and Schmitz et al (2000), thymidine incorporation was inhibited by higher concentrations of EPA (20 and 50 mg/ml, respectively). In the present study, EPA 2 mg/ml exhibited a significant anti-mitogenic effect.…”

“…It is plausible, therefore, that EPA may exert its effects through modulating mesangial proliferation. In support of this hypothesis, EPA has been shown to inhibit proliferation of a variety of cell lines including mesangial cells (Shiina et al, 1993;Finstad et al, 1994;Nitta et al, 1998;Schmitz et al, 2000). However, the exact mechanism of EPA's antimitogenic action has not been elucidated.…”

Eicosapentaenoic Acid Suppresses Basal and Insulin-Stimulated Endothelin-1 Production in Human Endothelial Cells

“…In cultured bovine mesangial cells (29), EPA has been reported to inhibit the production of ET-1. To date, however, there have been no reports of the effects of EPA on the production of ET-1 in human vascular endothelial cells.…”

“…On the other hand, benidipine inhibits the expression of ET-1 and TGF-β1 in Dahl saltsensitive hypertensive rats (28). In cultured bovine mesangial cells (29), EPA has been reported to inhibit mitogen-induced ET-1 production, but the effects of EPA on human endothelial cells and its underlying mechanism remain to be clarified.…”

A Vascular Approach to Glaucoma

“…Diets favouring omega-3 fatty acids, such as soy oils, instead of omega-6 fatty acids, such as corn or sunflower oils, have been associated with an increased risk for glaucoma (Kang, 2004). Considering its OBF-related effects, fish oil (rich in omega-6) improves circulation in patients with Raynaud's phenomenon (DiGiacomo, 1989) by inhibiting the endothelin-1 effect (Nitta, 1998). A number of dietary anti-oxidative agents, such as ginkgo biloba (Ritch, 2000), might also improve OBF.…”