Lysophosphatidylcholine modifies G protein-dependent signaling in porcine endothelial cells

Research output: Contribution to journalArticlepeer-review

Abstract

Certain endothelial receptors are coupled to a pertussis toxin-sensitive inhibitory guanine nucleotide-binding regulatory (G(i)) protein. In pigs, hypercholesterolemia causes a selective impairment of this G(i) protein- dependent pathway. Recent studies have suggested that hypercholesterolemia- induced endothelial dysfunction may be caused by lysophosphatidylcholine (LPC) derived from oxidized low-density lipoprotein (LDL). The aim of the present study was to determine whether LPC could inhibit the G(i) protein- dependent pathway. Isolated rings of porcine coronary arteries were suspended for isometric tension recording in organ chambers filled with physiological salt solution (37°C, 95% O2-5% CO2). In rings with endothelium contracted with prostaglandin F(2α), pertussis toxin (100 ng/ml) or LPC (10-5 M) inhibited the endothelium-dependent relaxations evoked by UK-14,304, an α2- adrenergic agonist, or by serotonin, but not those caused by bradykinin or ADP. LPC also did not inhibit relaxations produced by SIN 1, an endothelium- derived relaxing factor-nitric oxide donor. After treatment of the rings with pertussis toxin, LPC no longer inhibited the endothelium-dependent relaxations to serotonin. Although LPC inhibited the responses of membrane- bound receptors that activate the pertussis toxin-sensitive G(i) protein, LPC did not affect the endothelium-dependent relaxations evoked by direct activation of the pertussis toxin-sensitive G(i) protein by fluoride. These results suggest that LPC selectively inhibits a G(i) protein-dependent pathway in porcine endothelial cells possibly by disrupting receptor-G protein interactions. LPC that is associated with oxidized LDL may mediate in part the dysfunction in the endothelial G(i) protein-dependent pathway associated with hypercholesterolemia.

Original languageEnglish (US)
Pages (from-to)H722-H727
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume264
Issue number3 33-3
DOIs
StatePublished - 1993

Keywords

  • atherosclerosis
  • endothelium-derived relaxing factor
  • guanine nucleotide regulatory proteins
  • hypercholesterolemia
  • lipoproteins
  • porcine coronary artery

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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