In vitro angiogenic effects of pancreatic bile salt-dependent lipase.
OBJECTIVE
Bile salt-dependent lipase (BSDL), a lipolytic enzyme secreted in the duodenum by pancreatic acinar cells, has been detected in the serum of all patients and in atheromatous plaque, suggesting its potential implication in vascular pathophysiology.


RESULTS
In vitro pancreatic BSDL evokes human umbilical vein endothelial cell (HUVEC) proliferation and chemotactic migration. BSDL at mitogen concentration is capable to heal wounded HUVEC monolayer and to promote capillary network formation. HUVEC proliferation depends on the displacement of basic fibroblast growth factor and vascular endothelial growth factor from the extracellular matrix and the activation of extracellular signal-regulated kinases (ERK1/2), p38 mitogen-activated protein kinase, and focal adhesion kinase signaling pathways.


CONCLUSIONS
For the first time to our knowledge, it is suggested that circulating BSDL could be involved in pathophysiological angiogenesis. We delineate the in vitro effects of pancreatic BSDL on endothelial cells, and we show that BSDL promotes proliferation, migration, capillary network formation, and wound-healing of HUVECs via the displacement of bFGF and VEGF from the ECM, suggesting that BSDL could be involved in angiogenesis.
Rebaï
Ouafa
O
INSERM U-559 and IPHM, Marseille-cedex, France.
Le Petit-Thevenin
Josette
J
Bruneau
Nadine
N
Lombardo
Dominique
D
Vérine
Alain
A
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D003094:Collagen; D004261:DNA Replication / Q000187:drug effects; D004338:Drug Combinations; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D007797:Laminin; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008252:Macaca fascicularis; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D010179:Pancreas / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011509:Proteoglycans; D002787:Sterol Esterase / Q000494:pharmacology*; D014471:Umbilical Veins; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen; C054784:bile salt-stimulated lipase; D002787:Sterol Esterase