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

Area of Science:

• Cardiovascular Biology
• Molecular Pharmacology
• Endothelial Cell Function

Background:

• Linoleic acid (LA) promotes monocyte chemotaxis and adhesion molecules (MCP-1, VCAM-1), contributing to atherosclerosis.
• Endothelium-derived relaxing factors (EDRFs), like nitric oxide (NO) and prostaglandin I2 (PGI2), normally restrain these processes.
• The effect of LA on EDRF production is controversial, potentially linked to EDRF regulation by endothelial calcium (Ca2+) responses.

Purpose of the Study:

• To investigate the impact of LA and other free fatty acids on EDRF production.
• To examine the influence of LA on endothelial Ca2+ responses that mediate EDRF release.
• To elucidate the molecular mechanisms underlying LA's effects on EDRF production.

Main Methods:

• Primary cultured porcine aortic endothelial cells (PAECs) were utilized.
• Cells were treated with varying concentrations of LA and other fatty acids.
• Bradykinin (BK)-induced EDRF production, Ca2+ responses, and intracellular cyclic AMP (cAMP) levels were measured.
• In vitro assays assessed cAMP-hydrolyzing phosphodiesterase (PDE) activity.

Main Results:

• LA (0.1-5 μmol/L) dose-dependently attenuated BK-induced NO and PGI2 production in PAECs.
• LA suppressed BK-induced endothelial Ca2+ responses, an effect modulated by adenylate cyclase and PDE inhibitors.
• LA increased intracellular cAMP levels and selectively inhibited cAMP-hydrolyzing PDE activity in vitro.
• Palmitic, stearic, and oleic acids did not affect EDRF production or Ca2+ responses.

Conclusions:

• LA attenuates EDRF production and endothelial Ca2+ responses in PAECs.
• This effect is mediated by LA-induced intracellular cAMP accumulation through inhibition of cAMP-hydrolyzing PDE activity.
• LA's actions on EDRF production may contribute to its role in atherosclerotic processes.