Skip to main content
Erschienen in: Angiogenesis 3/2008

01.09.2008 | Original Paper

Lysophosphatidic acid (LPA) and angiogenesis

verfasst von: Carol M. Rivera-Lopez, Amy L. Tucker, Kevin R. Lynch

Erschienen in: Angiogenesis | Ausgabe 3/2008

Einloggen, um Zugang zu erhalten

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
Literatur
1.
Zurück zum Zitat English D, Kovala AT, Welch Z, Harvey KA, Siddiqui RA, Brindley DN, Garcia JG (1999) Induction of endothelial cell chemotaxis by sphingosine 1-phosphate and stabilization of endothelial monolayer barrier function by LPA, potential mediators of hematopoietic angiogenesis. J Hematother Stem Cell Res 8(6):627–634PubMedCrossRef English D, Kovala AT, Welch Z, Harvey KA, Siddiqui RA, Brindley DN, Garcia JG (1999) Induction of endothelial cell chemotaxis by sphingosine 1-phosphate and stabilization of endothelial monolayer barrier function by LPA, potential mediators of hematopoietic angiogenesis. J Hematother Stem Cell Res 8(6):627–634PubMedCrossRef
2.
Zurück zum Zitat Duriex ME, Lynch KR (1993) Signaling properties of lysophosphatidic acid. Trends Pharmacol Sci 14:249–254CrossRef Duriex ME, Lynch KR (1993) Signaling properties of lysophosphatidic acid. Trends Pharmacol Sci 14:249–254CrossRef
3.
Zurück zum Zitat Goodemote KA, Mattie ME, Berger A, Spiegel S (1995) Involvement of a pertussis toxin-sensitive G protein in the mitogenic signaling pathways of sphingosine–1-phosphate. J Biol Chem 270:10272–10277PubMedCrossRef Goodemote KA, Mattie ME, Berger A, Spiegel S (1995) Involvement of a pertussis toxin-sensitive G protein in the mitogenic signaling pathways of sphingosine–1-phosphate. J Biol Chem 270:10272–10277PubMedCrossRef
4.
Zurück zum Zitat Ridley AJ, Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399PubMedCrossRef Ridley AJ, Hall A (1992) The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399PubMedCrossRef
5.
Zurück zum Zitat Postma FR, Jalink K, Hengeveld T, Moolenar WH (1996) Sphingosine-1-phosphate rapidly induces rho-dependent neurite retraction: action through a specific cell surface receptor. EMBO J 15:2388–2395PubMed Postma FR, Jalink K, Hengeveld T, Moolenar WH (1996) Sphingosine-1-phosphate rapidly induces rho-dependent neurite retraction: action through a specific cell surface receptor. EMBO J 15:2388–2395PubMed
6.
Zurück zum Zitat Noguchi K, Ishii S, Shimizu T (2003) Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J Biol Chem 278:25600–25606PubMedCrossRef Noguchi K, Ishii S, Shimizu T (2003) Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J Biol Chem 278:25600–25606PubMedCrossRef
7.
Zurück zum Zitat Lee CW, Rivera R, Gardell S, Dubin AE, Chun J (2006) GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J Biol Chem 281:23589–23597PubMedCrossRef Lee CW, Rivera R, Gardell S, Dubin AE, Chun J (2006) GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J Biol Chem 281:23589–23597PubMedCrossRef
8.
Zurück zum Zitat Van Koppen CJ, Heringdorf DMZ, Laser KT, Zhang CY, Jakobs KH, Bunemann M, Pott L (1996) Activation of a high affinity Gi protein-coupled plasma membrane receptor by sphingosine 1-phosphate. J Biol Chem 271:2082–2087PubMedCrossRef Van Koppen CJ, Heringdorf DMZ, Laser KT, Zhang CY, Jakobs KH, Bunemann M, Pott L (1996) Activation of a high affinity Gi protein-coupled plasma membrane receptor by sphingosine 1-phosphate. J Biol Chem 271:2082–2087PubMedCrossRef
9.
Zurück zum Zitat Fromm C, Coso OA, Montaner S, Xu N, Gutkind JS (1997) The small GTP-binding protein Rho links G protein-coupled receptors and Galpha 12 to the serum response element and to cellular transformation. Proc Natl Acad Sci USA 94:10098–10103PubMedCrossRef Fromm C, Coso OA, Montaner S, Xu N, Gutkind JS (1997) The small GTP-binding protein Rho links G protein-coupled receptors and Galpha 12 to the serum response element and to cellular transformation. Proc Natl Acad Sci USA 94:10098–10103PubMedCrossRef
10.
Zurück zum Zitat Ghosh S, Strum JC, Bell RM (1997) Lipid biochemistry: functions of glycerolipids and sphingolipids in cellular signaling. FASEB J 11:45–50PubMed Ghosh S, Strum JC, Bell RM (1997) Lipid biochemistry: functions of glycerolipids and sphingolipids in cellular signaling. FASEB J 11:45–50PubMed
11.
Zurück zum Zitat Bian D, Su S, Mahanivong C, Cheng RK, Han Q, Pan ZK, Sun P, Huang S (2004) Lysophosphatidic acid stimulates ovarian cancer cell migration via a Ras-MEK kinase 1 pathway. Cancer Res 64:4209–4217PubMedCrossRef Bian D, Su S, Mahanivong C, Cheng RK, Han Q, Pan ZK, Sun P, Huang S (2004) Lysophosphatidic acid stimulates ovarian cancer cell migration via a Ras-MEK kinase 1 pathway. Cancer Res 64:4209–4217PubMedCrossRef
12.
Zurück zum Zitat Contos JJ, Ishii I, Fukushima N, Kingsbury MA, Ye X, Kawamura S, Brown JH, Chun J (2002) Characterization of lpa2 (Edg4) and lpa1/lpa2 (Edg4/Edg2) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa2. Mol Cell Biol 22:6921–6929PubMedCrossRef Contos JJ, Ishii I, Fukushima N, Kingsbury MA, Ye X, Kawamura S, Brown JH, Chun J (2002) Characterization of lpa2 (Edg4) and lpa1/lpa2 (Edg4/Edg2) lysophosphatidic acid receptor knockout mice: signaling deficits without obvious phenotypic abnormality attributable to lpa2. Mol Cell Biol 22:6921–6929PubMedCrossRef
13.
Zurück zum Zitat Ye X, Hama K, Contos JJ, Anliker B, Inoue A, Skinner MK, Suzuki H, Amano T, Kennedy G, Arai H, Aoki J, Chun J (2005) LPA3-mediated lysophosphatidic acid signaling in embryo implantation and spacing. Nature 435:104–108PubMedCrossRef Ye X, Hama K, Contos JJ, Anliker B, Inoue A, Skinner MK, Suzuki H, Amano T, Kennedy G, Arai H, Aoki J, Chun J (2005) LPA3-mediated lysophosphatidic acid signaling in embryo implantation and spacing. Nature 435:104–108PubMedCrossRef
14.
Zurück zum Zitat Baker DL, Desiderio DM, Miller DD, Tolley B, Tigyi GJ (2001) Direct quantitative analysis of lysophosphatidic acid molecular species by stable isotope dilution electrospray ionization liquid chromatography-mass spectrometry. Anal Biochem 292:287–295PubMedCrossRef Baker DL, Desiderio DM, Miller DD, Tolley B, Tigyi GJ (2001) Direct quantitative analysis of lysophosphatidic acid molecular species by stable isotope dilution electrospray ionization liquid chromatography-mass spectrometry. Anal Biochem 292:287–295PubMedCrossRef
15.
Zurück zum Zitat Saulnier-Blache JS, Girard A, Simon MF, Lafontan M, Valet P (2000) A simple and highly sensitive radioenzymatic assay for lysophosphatidic acid quantification. J Lipid Res 41:1947–1951PubMed Saulnier-Blache JS, Girard A, Simon MF, Lafontan M, Valet P (2000) A simple and highly sensitive radioenzymatic assay for lysophosphatidic acid quantification. J Lipid Res 41:1947–1951PubMed
16.
Zurück zum Zitat Pages C, Simon MF, Valet P, Saulnier-Blache JS (2001) Lysophosphatidic acid synthesis and release. Prostaglandins Other Lipid Mediat 64:1–10PubMedCrossRef Pages C, Simon MF, Valet P, Saulnier-Blache JS (2001) Lysophosphatidic acid synthesis and release. Prostaglandins Other Lipid Mediat 64:1–10PubMedCrossRef
17.
Zurück zum Zitat Saba JD (2004) Lysophospholipids in development: miles apart and edging in. J Cell Biochem 92:967–992PubMedCrossRef Saba JD (2004) Lysophospholipids in development: miles apart and edging in. J Cell Biochem 92:967–992PubMedCrossRef
18.
Zurück zum Zitat Lee H, Goetzl EJ, An S (2000) Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing. Am J Physiol Cell Physiol 278:C612–C618PubMed Lee H, Goetzl EJ, An S (2000) Lysophosphatidic acid and sphingosine 1-phosphate stimulate endothelial cell wound healing. Am J Physiol Cell Physiol 278:C612–C618PubMed
19.
Zurück zum Zitat English D, Kovala AT, Welch Z, Harvey KA, Siddiqui RA, Brindley DN, Garcia JG (1999) Induction of endothelial cell chemotaxis by sphingosine 1-phosphate and stabilization of endothelial monolayer barrier function by lysophosphatidic acid, potential mediators of hematopoietic angiogenesis. J Hematother Stem Cell Res 8(6):627–634PubMedCrossRef English D, Kovala AT, Welch Z, Harvey KA, Siddiqui RA, Brindley DN, Garcia JG (1999) Induction of endothelial cell chemotaxis by sphingosine 1-phosphate and stabilization of endothelial monolayer barrier function by lysophosphatidic acid, potential mediators of hematopoietic angiogenesis. J Hematother Stem Cell Res 8(6):627–634PubMedCrossRef
20.
Zurück zum Zitat Wu WT, Chen CN, Lin CI, Chen JH, Lee H (2005) Lysophospholipids enhance matrix metalloproteinase-2 expression in human endothelial cells. Endocrinology 146:3387–3400PubMedCrossRef Wu WT, Chen CN, Lin CI, Chen JH, Lee H (2005) Lysophospholipids enhance matrix metalloproteinase-2 expression in human endothelial cells. Endocrinology 146:3387–3400PubMedCrossRef
21.
Zurück zum Zitat Nam SW, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA, Stracke ML (2001) Autotaxin (NPP–2), a metastasis-enhancing mitogen, is an angiogenic factor. Cancer Res 61:6938–6944PubMed Nam SW, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA, Stracke ML (2001) Autotaxin (NPP–2), a metastasis-enhancing mitogen, is an angiogenic factor. Cancer Res 61:6938–6944PubMed
22.
Zurück zum Zitat van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, Pettit TR, Wakelam MJO, Saulnier-Blache JS, Mummery CL, Moolenaar WH, Jonkers J (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26(13):5015–5022PubMedCrossRef van Meeteren LA, Ruurs P, Stortelers C, Bouwman P, van Rooijen MA, Pradere JP, Pettit TR, Wakelam MJO, Saulnier-Blache JS, Mummery CL, Moolenaar WH, Jonkers J (2006) Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. Mol Cell Biol 26(13):5015–5022PubMedCrossRef
23.
Zurück zum Zitat Sabbadini RA (2006) Targeting sphingosine-1-phosphate for cancer therapy. Br J Cancer 95:1131–1135PubMedCrossRef Sabbadini RA (2006) Targeting sphingosine-1-phosphate for cancer therapy. Br J Cancer 95:1131–1135PubMedCrossRef
24.
Zurück zum Zitat Heasley BH, Jarosz R, Lynch KR, Macdonald TL (2004) Initial structure-activity relationships of lysophosphatidic acid receptor antagonist: discovery of a high-affinity LPA1/LPA3 receptor antagonist. Bioorg Med Chem Lett 14:2735–2740PubMedCrossRef Heasley BH, Jarosz R, Lynch KR, Macdonald TL (2004) Initial structure-activity relationships of lysophosphatidic acid receptor antagonist: discovery of a high-affinity LPA1/LPA3 receptor antagonist. Bioorg Med Chem Lett 14:2735–2740PubMedCrossRef
25.
Zurück zum Zitat Hasegawa Y, Erickson JR, Goddard GJ, Yu S, Liu S, Cheng KW, Eder A, Bandoh K, Aoki J, Jarosz R, Schrier AD, Lynch KR, Mills GB, Fang X (2003) Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J Biol Chem 278:11962–11969PubMedCrossRef Hasegawa Y, Erickson JR, Goddard GJ, Yu S, Liu S, Cheng KW, Eder A, Bandoh K, Aoki J, Jarosz R, Schrier AD, Lynch KR, Mills GB, Fang X (2003) Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor. J Biol Chem 278:11962–11969PubMedCrossRef
26.
Zurück zum Zitat Lee S, Lynch KR (2005) Brown recluse spider (Loxosceles reclusa) venom phospholipase D (PLD) generates lysophosphatidic acid (LPA). Biochem J 391:317–323PubMedCrossRef Lee S, Lynch KR (2005) Brown recluse spider (Loxosceles reclusa) venom phospholipase D (PLD) generates lysophosphatidic acid (LPA). Biochem J 391:317–323PubMedCrossRef
27.
Zurück zum Zitat van Meeteren LA, Frederiks F, Giepmans BN, Pedrosa MF, Billington SJ, Jost BH, Tambourgi DV, Moolenaar WH (2004) Spider and bacterial sphingomyelinases D target cellular lysophosphatidic acid receptors by hydrolyzing lysophosphatidylcholine. J Biol Chem 279(12):10833–10836PubMedCrossRef van Meeteren LA, Frederiks F, Giepmans BN, Pedrosa MF, Billington SJ, Jost BH, Tambourgi DV, Moolenaar WH (2004) Spider and bacterial sphingomyelinases D target cellular lysophosphatidic acid receptors by hydrolyzing lysophosphatidylcholine. J Biol Chem 279(12):10833–10836PubMedCrossRef
28.
Zurück zum Zitat Goetzl EJ, An S (1998) Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB J 12:1589–1598PubMed Goetzl EJ, An S (1998) Diversity of cellular receptors and functions for the lysophospholipid growth factors lysophosphatidic acid and sphingosine 1-phosphate. FASEB J 12:1589–1598PubMed
29.
Zurück zum Zitat Koutrafouri V, Leondiadis L, Avgoustakis K, Livaniou E, Czarnecki J, Ithakissios DS, Evangelatos GP (2001) Effect of thymosin peptides on the chick chorioallantoic membrane angiogenesis model. Biochim Biophys Acta 1568:60–66PubMed Koutrafouri V, Leondiadis L, Avgoustakis K, Livaniou E, Czarnecki J, Ithakissios DS, Evangelatos GP (2001) Effect of thymosin peptides on the chick chorioallantoic membrane angiogenesis model. Biochim Biophys Acta 1568:60–66PubMed
30.
Zurück zum Zitat Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286PubMedCrossRef Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286PubMedCrossRef
31.
Zurück zum Zitat Chen CH, Walterscheid JP (2006) Plaque angiogenesis versus compensatory arteriogenesis in atherosclerosis. Circ Res 99:787–789PubMedCrossRef Chen CH, Walterscheid JP (2006) Plaque angiogenesis versus compensatory arteriogenesis in atherosclerosis. Circ Res 99:787–789PubMedCrossRef
32.
Metadaten
Titel
Lysophosphatidic acid (LPA) and angiogenesis
verfasst von
Carol M. Rivera-Lopez
Amy L. Tucker
Kevin R. Lynch
Publikationsdatum
01.09.2008
Verlag
Springer Netherlands
Erschienen in
Angiogenesis / Ausgabe 3/2008
Print ISSN: 0969-6970
Elektronische ISSN: 1573-7209
DOI
https://doi.org/10.1007/s10456-008-9113-5

Weitere Artikel der Ausgabe 3/2008

Angiogenesis 3/2008 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Schadet Ärger den Gefäßen?

14.05.2024 Arteriosklerose Nachrichten

In einer Studie aus New York wirkte sich Ärger kurzfristig deutlich negativ auf die Endothelfunktion gesunder Probanden aus. Möglicherweise hat dies Einfluss auf die kardiovaskuläre Gesundheit.

Intervallfasten zur Regeneration des Herzmuskels?

14.05.2024 Herzinfarkt Nachrichten

Die Nahrungsaufnahme auf wenige Stunden am Tag zu beschränken, hat möglicherweise einen günstigen Einfluss auf die Prognose nach akutem ST-Hebungsinfarkt. Darauf deutet eine Studie an der Uniklinik in Halle an der Saale hin.

Klimaschutz beginnt bei der Wahl des Inhalators

14.05.2024 Klimawandel Podcast

Auch kleine Entscheidungen im Alltag einer Praxis können einen großen Beitrag zum Klimaschutz leisten. Die neue Leitlinie zur "klimabewussten Verordnung von Inhalativa" geht mit gutem Beispiel voran, denn der Wechsel vom klimaschädlichen Dosieraerosol zum Pulverinhalator spart viele Tonnen CO2. Leitlinienautor PD Dr. Guido Schmiemann erklärt, warum nicht nur die Umwelt, sondern auch Patientinnen und Patienten davon profitieren.

Zeitschrift für Allgemeinmedizin, DEGAM

Typ-2-Diabetes und Depression folgen oft aufeinander

14.05.2024 Typ-2-Diabetes Nachrichten

Menschen mit Typ-2-Diabetes sind überdurchschnittlich gefährdet, in den nächsten Jahren auch noch eine Depression zu entwickeln – und umgekehrt. Besonders ausgeprägt ist die Wechselbeziehung laut GKV-Daten bei jüngeren Erwachsenen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.