Linoleic acid attenuates endothelium-derived relaxing factor production by suppressing cAMP-hydrolyzing phosphodiesterase activity

Background: Linoleic acid (LA) promotes monocyte chemotaxis and cell adhesion molecules such as MCP-1 and VCAM-1, which contribute to atherosclerogenesis. These molecules are restrained by endothelium-derived relaxing factors (EDRFs), such as nitric oxide (NO) and prostaglandin I2 (PGI2). Hence, the expressions of MCP-1 and VCAM-1 upregulated by LA may be partly attributable to decreased EDRF production. However, effect of LA on EDRF production remains controversial. Methods and Results: The present study aimed to examine the effects of LA and other free fatty acids on EDRF production and the endothelial Ca2+ responses that mediate EDRF production, using primary cultured porcine aortic endothelial cells (PAECs). LA at 0.1–5 μmol/L attenuated bradykinin (BK)-induced NO and PGI2 production while suppressing the BK-induced Ca2+ response dose-dependently. The inhibitory effect of LA on the Ca2+ response was eliminated by adenylate cyclase inhibitor SQ22536, boosted by cAMP-hydrolyzing phosphodiesterase (PDE) inhibitor, rolipram, and mimicked by plasma membrane permeable 8-bromo-cAMP. Moreover, LA was confirmed to dose-dependently increase intracellular cAMP levels and selectively inhibit cAMP-hydrolyzing PDE activity in vitro.In contrast, none of palmitic, stearic, or oleic acid affected BK-induced EDRF production or Ca2+ responses, or induced intracellular cAMP accumulation. Conclusions: LA induced intracellular cAMP accumulation by inhibiting cAMP-hydrolyzing PDE activity, thus resulting in attenuation of Ca2+ responses and EDRF production in PAECs.;浜松医科大学学位論文 医博第685号(平成26年9月19日);開始ページ : 2823;終了ページ : 2830;PubMed番号 : info:pmid/23883876

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書名 Linoleic acid attenuates endothelium-derived relaxing factor production by suppressing cAMP-hydrolyzing phosphodiesterase activity
著作者等 日本循環器学会
Wei Jiazhang
韦 嘉章
書名別名 リノール酸はcAMP加水分解型ホスホジエステラーゼ阻害を介して内皮由来血管弛緩因子産生を抑制する
出版元 Japanese Circulation Society
刊行年月 2001.12-
ページ数 v.
大きさ 26 cm
ISSN 13469843
NCID AA11591968
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全国書誌番号
10057473
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言語 英語
出版国 日本
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