Pancreatic bile salt-dependent lipase induces smooth muscle cells proliferation.
BACKGROUND
Because bile salt-dependent lipase (BSDL), an enzyme secreted by the pancreatic acinar cells and associated with LDL in circulating blood, also locates with smooth muscle cells (SMCs) in atherosclerotic lesions, we aimed to investigate its effects on SMCs.


RESULTS
Immunohistochemical experiments allowed us to detect an expression of BSDL in atherosclerotic lesions from hypercholesterolemic monkeys and from human arteries. BSDL was found to be associated with SMCs but not with macrophages. BSDL was significantly mitogenic for cultured SMCs. This effect was inhibited by heparin and anti-BSDL antibodies, whereas heat-denaturated and diisopropylfluorophosphate-treated BSDL were inefficient. The mitogenic effect of BSDL was associated with an activation of the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway, which was inhibited by heparin, and involved several mechanisms, among them diacylglycerol and oleic acid production as well as a rapid basic fibroblast growth factor release.


CONCLUSIONS
Circulating BSDL is associated with SMCs within the intimal arteria and may trigger SMC proliferation, which could contribute to the development of atherosclerotic lesions.
Augé
Nathalie
N
INSERM U-466, Marseille, France.
Rebaï
Ouafa
O
Lepetit-Thévenin
Josette
J
Bruneau
Nadine
N
Thiers
Jean-Claude
JC
Mas
Eric
E
Lombardo
Dominique
D
Negre-Salvayre
Anne
A
Vérine
Alain
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000201:enzymology / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications / Q000201:enzymology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000201:enzymology; D007150:Immunohistochemistry; D007531:Isoflurophate / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010179:Pancreas / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015290:Second Messenger Systems / Q000187:drug effects; D002787:Sterol Esterase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000494:pharmacology*
D000906:Antibodies; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D007531:Isoflurophate; C054784:bile salt-stimulated lipase; D002787:Sterol Esterase