Linoleic Acid Attenuates Endothelium-Derived Relaxing Factor Production by Suppressing cAMP-Hydrolyzing Phosphodiesterase Activity

• Wei Jiazhang

  Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine

• Takeuchi Kazuhiko

  Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine

• Watanabe Hiroshi

  Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine

抄録

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.  (Circ J 2013; 77: 2823–2830)<br>

収録刊行物

• Circulation Journal

  Circulation Journal 77 (11), 2823-2830, 2013

  一般社団法人 日本循環器学会

キーワード

• Cyclic AMP
• Endothelial cells
• Endothelium-derived relaxing factor
• Linoleic acid
• Phosphdiesterase

詳細情報

• CRID: 1390001205102081024
• NII論文ID: 10031196837
• NII書誌ID: AA11591968
• DOI: 10.1253/circj.cj-13-0248
• COI: 1:CAS:528:DC%2BC3sXhvVamtL3M
• ISSN: 13474820
• ISSN: 13469843
• PubMed: 23883876
• Web Site: https://www.jstage.jst.go.jp/article/circj/77/11/77_CJ-13-0248/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2014247707
• 本文言語コード: en
• データソース種別:
  • JaLC
  • Crossref
  • PubMed
  • CiNii Articles
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