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Lysophosphatidic acid (LPA) and angiogenesis

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Abstract

Lysophosphatidic acid (LPA) is a simple lipid with many important biological functions such as the regulation of cellular proliferation, cellular migration, differentiation, and suppression of apoptosis. Although a direct angiogenic effect of LPA has not been reported to date, there are indications that LPA promotes angiogenesis. In addition, LPA is a chemoattractant for cultured endothelial cells and promotes barrier function in such cultures [1]. To test the hypothesis that LPA is angiogenic, we used the chicken chorio-allantoic membrane (CAM) assay. Sequence analysis of the cloned, full-length chicken LPA receptor cDNAs revealed three receptor types that are orthologous to the mammalian LPA1, LPA2, and LPA3 receptors. We document herein that LPA is angiogenic in the CAM system and further that synthetic LPA receptor agonists and antagonists mimic or block this response, respectively. Our results predict that LPA receptor antagonists are a possible therapeutic route to interdicting angiogenesis

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Acknowledgments

We want to thank Sangderk Lee, Ph.D. (Lynch laboratory) for providing us with helpful advice for cloning the chicken LPA receptors.

Funding sources

This work was supported by research grants from the National Institutes of Health (R01 GM052722 (KRL) and F31 HL079881 (CRL).

Disclosures

VPC32183 is sold by Avanti Polar Lipids under license from the University of Virginia.

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Authors and Affiliations

  1. Department of Pharmacology, University of Virginia, School of Medicine, Box 800735, 1340 Jefferson Park Avenue, Charlottesville, VA, 22903-0735, USA

    Carol M. Rivera-Lopez & Kevin R. Lynch

  2. Department of Medicine, University of Virginia, Charlottesville, VA, 22908, USA

    Amy L. Tucker

  3. Department of Cardiovascular Research Center (CVRC), University of Virginia, Charlottesville, VA, 22908, USA

    Amy L. Tucker

Authors
  1. Carol M. Rivera-Lopez
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  2. Amy L. Tucker
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  3. Kevin R. Lynch
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Correspondence to Kevin R. Lynch.

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Rivera-Lopez, C.M., Tucker, A.L. & Lynch, K.R. Lysophosphatidic acid (LPA) and angiogenesis. Angiogenesis 11, 301–310 (2008). https://doi.org/10.1007/s10456-008-9113-5

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  • DOI: https://doi.org/10.1007/s10456-008-9113-5

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