Primary human endothelial cells secrete agents that reduce responsiveness to lysophosphatidic acid (LPA).
The plasma level of LPA (lysophosphatidic acid) (200-600 nM) is well within the range that promotes proliferation and migration of vascular ECs (endothelial cells), yet vessels are quiescent and stable. In this report, we considered one explanation for this paradox: that ECs secrete agents that attenuate responsiveness to LPA. Indeed, we observed that CM (conditioned medium) from confluent, quiescent cultures of primary HUVECs (human umbilical vein ECs) contained an agent that inhibited LPA-mediated signalling events and cellular responses. The putative inhibitor, which we tentatively call ILMR (inhibitor of LPA-mediated responsiveness) seemed to act on cells (instead of at the level of LPA) by suppressing the ability of LPA receptor 1 to signal. The amount and/or activity of ILMR was regulated by growth factors; exposing HUVECs to VEGF-A (vascular endothelial growth factor A), but not bFGF (basic fibroblast growth factor), reduced the amount and/or activity of ILMR in CM. We conclude that in addition to promoting angiogenesis directly, VEGF-A can also act indirectly by modulating the bioactivity of angiomodulators such as LPA.
Schepens Eye Research Institute, Massachusetts Eye and Ear Infirmary, Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
Eun Young
EY
Park
Andrius
A
Kazlauskas
D043925:Angiogenesis Inducing Agents / Q000037:antagonists & inhibitors; D020533:Angiogenesis Inhibitors / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D017077:Culture Media, Conditioned; D016222:Fibroblast Growth Factor 2 / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000502:physiology*; D055806:Microvessels / Q000166:cytology; D051419:Paxillin / Q000378:metabolism; D010766:Phosphorylation; D061251:Primary Cell Culture; D051381:Rats; D012867:Skin / Q000098:blood supply; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D017077:Culture Media, Conditioned; D008246:Lysophospholipids; C496061:PXN protein, human; D051419:Paxillin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C032881:lysophosphatidic acid