Induction of cyclooxygenase-2 in human umbilical vein endothelial cells by lysophosphatidylcholine.

Abstract

Lysophosphatidyicholine (lysoPC), a component of atherogenic lipoproteins and atherosclerotic lesions, has been recently suggested to play a role in atherogenesis. LysoPC is known to induce several endothelial genes involved in leukocyte recruitment, mitogenesis, and inflammation. Cyclooxygenases (prostaglandin H2 synthases) are rate-limiting enzymes involved in the endothelial synthesis of prostacyclin, an antiplatelet, vasorelaxant, and vasoprotective molecule. We investigated the effect of lysoPC on the endothelial expression of cyclooxygenases. Our results demonstrate that, in cultured human umbilical vein endothelial cells, lysoPC induces cyclooxygenase-2 mRNA and protein levels. Increased expression of cyclooxygenase-2 is accompanied by the enhancement of both basal-and calcium ionophore A23187-induced synthesis of prostacyclin. Nuclear runoff experiments demonstrated an increased rate of transcription of the cyclooxygenase-2 gene by lysoPC. In contrast, lysoPC did not affect the expression of constitutive cyclooxygenase-1. Our results suggest that the induction of endothelial cyclooxygenase-2 by lysoPC may be an important vasoprotective mechanism that limits progression of atherosclerotic lesions and promotes their regression. (J.

Lysophosphatidylcholine Stimulates Activator Protein 1 and the c-Jun N-terminal Kinase Activity

“…As shown in Fig. 3, no mobility shift of ERK2 was observed in cells treated with different concentrations of lyso-PC (1, 10, and 20 M) for different intervals (5,10,15,20, and 25 min). In contrast, such a mobility shift was readily detected in the cells treated with known MAPK stimulators, TPA and lyso-PA.…”

“…The addition of lyso-PC to cultured cells can transcriptionally up-regulate the expression of a variety of genes including cell adhesion molecules (intercellular adhesion molecule 1 and vascular cell adhesion molecule 1) (10), growth factors (platelet-derived growth factors A and B and heparin-binding epidermal growth factor) (11,12), and vasoprotective enzymes such as nitric-oxide synthase (13,14) and cyclooxygenase-2 (15). In vascular smooth muscle, lyso-PC has been shown to induce vascular relaxation (16,17) and to stimulate cell proliferation (18,19).…”

Lysophosphatidylcholine Potentiates the Mitogenic Effect of Various Vasoactive Compounds on Rabbit Aortic Smooth Muscle Cells.

“…5,[24][25][26][27][28] In VSMCs, lyso-PC has been shown to be toxic to cells at high concentrations while lower concentrations induce DNA synthesis and cell growth, which over a narrow concentration range can cause both cytotoxic and proliferative effects. 7,11) Several investigators have reported that G protein-mediated signal transduction is impaired by high levels of lyso-PC.…”

Involvement of Oxysterols and Lysophosphatidylcholine in the Oxidized LDL–Induced Impairment of Serum Albumin Synthesis by HEPG2 Cells

“…44 Several research groups have demonstrated that LPC alters various endothelial functions and induces several endothelial genes expressed in the atherosclerotic arterial wall. Reports describe the induction of intracellular adhesion molecule-1, macrophage chemoattractant protein-1, cyclooxygenase-2, and growth factors in endothelial cells, 16,17 possibly through modulation of transcription of nuclear factor B via a protein kinase C-mediated pathway. 45 However, some reports suggest that Ox-LDL has opposing effects on the activities of transcription factor activator protein-1, suggesting involvement of mechanisms for transcriptional regulation that are strongly affected by oxysterols rather than LPC.…”

“…Lysophosphatidylcholine (LPC) has been reported to mediate several of the proinflammatory effects of oxidized LDL (Ox-LDL), to stimulate smooth muscle cell proliferation, and to induce several endothelial genes expressed in the atherosclerotic arterial wall. 16,17 LPC, which has also been identified in experimentally induced atherosclerotic lesions in animals, has been shown to be chemotactic. 18 Albumin represents the most abundant serum protein, with normal concentrations lying between 35 and 50 g/L.…”