Migration of vascular smooth muscle cells induced by sphingosine 1-phosphate and related lipids: potential role in the angiogenic response.
The bioactive lipids sphingosine 1-phosphate (SPP), sphingosylphosphorylcholine, and lysophosphatidic acid play an important role in angiogenesis as a result of their effects on both the migration of endothelial cells (ECs) and the integrity of EC monolayers. Here we show that extremely low concentrations of serum and nanomolar concentrations of these biologically active lipids stimulate migration of human aortic smooth muscle cells (SMCs). However, at dosages most effective in promoting EC migration and in enhancing EC monolayer integrity, serum and SPP potently inhibited SMC migration; SPP also blocked the migration induced by protein growth factors. Treatment of SMCs with SPP induced transient phosphorylation of a 175- to 185-kDa protein corresponding to the PDGF receptor, indicating transactivation of this receptor. SPP and related lipids may play a key role in angiogenesis by coordinating the migration of both endothelial cells and vascular smooth muscle cells in response to the changing gradients of these bioactive lipid messengers.
Boguslawski
George
G
Experimental Cell Research Laboratory, Methodist Research Institute, Indianapolis, Indiana 46202, USA.
Grogg
Jeremy R
JR
Welch
Zachary
Z
Ciechanowicz
Sandra
S
Sliva
Daniel
D
Kovala
A Thomas
AT
McGlynn
Patrick
P
Brindley
David N
DN
Rhoades
Rodney A
RA
English
Denis
D
D001798:Blood Proteins / Q000378:metabolism / Q000494:pharmacology; D002450:Cell Communication / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004727:Endothelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066246:ErbB Receptors / Q000187:drug effects / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D008246:Lysophospholipids; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010743:Phospholipids / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001798:Blood Proteins; D006133:Growth Substances; D008246:Lysophospholipids; D010743:Phospholipids; D010566:Virulence Factors, Bordetella; C060506:sphingosine 1-phosphate; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor; D013110:Sphingosine