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Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells

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Abstract

Lysophosphatidylcholine (LPC) is the major bioactive lipid component of oxidized LDL, thought to be responsible for many of the inflammatory effects of oxidized LDL described in both inflammatory and endothelial cells. Inflammation-induced transformation of vascular smooth muscle cells from a contractile phenotype to a proliferative/secretory phenotype is a hallmark of the vascular remodeling that is characteristic of atherogenesis; however, the role of LPC in this process has not been fully described. The present study tested the hypothesis that LPC is an inflammatory stimulus in coronary artery smooth muscle cells (CASMCs). In cultured human CASMCs, LPC stimulated time- and concentration-dependent release of arachidonic acid that was sensitive to phospholipase A2 and C inhibition. LPC stimulated the release of arachidonic acid metabolites leukotriene-B4 and 6-keto-prostaglandin F1α, within the same time course. LPC was also found to stimulate basic fibroblast growth factor release as well as stimulating the release of the cytokines GM-CSF, IL-6, and IL-8. Optimal stimulation of these signals was obtained via palmitic acid-substituted LPC species. Stimulation of arachidonic acid, inflammatory cytokines and growth factor release, implies that LPC might play a multifactorial role in the progression of atherosclerosis, by affecting inflammatory processes.

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Acknowledgment

We thank Carol D. Manning for cytokine measurement.

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Authors and Affiliations

  1. Department of Vascular Biology and Thrombosis, Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA, 19406, USA

    Nambi Aiyar, Jyoti Disa, Zhaohui Ao, Colin H. Macphee, Douglas G. Johns & Stephen A. Douglas

  2. Department of Investigative Biology, Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, PA, 19406, USA

    Sandhya Nerurkar & Robert N. Willette

  3. Department of Safety Assessment, Cardiovascular and Urogenital Center of Excellence for Drug Discovery, GlaxoSmithKline, King of Prussia, PA, 19406, USA

    Haisong Ju

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  1. Nambi Aiyar
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Correspondence to Nambi Aiyar.

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Aiyar, N., Disa, J., Ao, Z. et al. Lysophosphatidylcholine induces inflammatory activation of human coronary artery smooth muscle cells. Mol Cell Biochem 295, 113–120 (2007). https://doi.org/10.1007/s11010-006-9280-x

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  • DOI: https://doi.org/10.1007/s11010-006-9280-x

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