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

• Material Type: 博士論文
• ISSN: 1346-9843
• Title: Linoleic acid attenuates endothelium-derived relaxing factor production by suppressing cAMP-hydrolyzing phosphodiesterase activity
• Volume: 77 11
• Author/Editor: 韦, 嘉章
• Author Heading: 韦, 嘉章
• Publication, Distribution, etc.: 日本循環器学会
• Publication Date: 2013-11
• Publication Date (W3CDTF): 2013-11
• Alternative Title: 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
• Periodical title: Circulation Journal
• Degree grantor/type: 浜松医科大学
• Date Granted: 2014-09-19
• Date Granted (W3CDTF): 2014-09-19
• Dissertation Number: 甲第685号
• Degree Type: 博士（医学）
• Conferring No. (Dissertation): 甲第685号
• Text Language Code: eng
• Subject Heading: Cyclic AMP; Endothelial cells; Endothelium-derived relaxing factor; Linoleic acid; Phosphdiesterase
• Target Audience: 一般
• Note (General): doctoral; 医学系研究科; 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 0.1-5μmol/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.
• DOI: info:doi/10.1253/circj.CJ-13-0248; https://doi.org/info:doi/10.1253/circj.CJ-13-0248
• Persistent ID (NDL): info:ndljp/pid/9491467; https://dl.ndl.go.jp/pid/9491467
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2015-09-01T13:12:47+09:00
• Date Created (W3CDTF): 2018-08-27
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
• Service for the Digitized Contents Transmission Service: 図書館・個人送信対象外
• Availability of remote photoduplication service: 可
• Periodical Title (URI): http://hdl.handle.net/10271/2877; https://hama-med.repo.nii.ac.jp/records/2743
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp