Published Online
on June 23, 2003

A more recent version of this article appeared on July 8, 2003

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Submitted on December 31, 2002
Revised on March 14, 2003
Accepted on March 26, 2003

Pancreatic Bile Salt-Dependent Lipase Induces Smooth Muscle Cells Proliferation

Nathalie Augé PhD, Ouafa Rebaï MS, Josette Lepetit-Thévenin MS, Nadine Bruneau PhD, Jean-Claude Thiers PhD, Eric Mas PhD, Dominique Lombardo PhD^*, Anne Negre-Salvayre PhD, and Alain Vérine PhD

From INSERM U-466 (N.A., J.C.T., A.N.S.), CHU Rangueil, Toulouse, and INSERM U-559 (O.R., J.L.T., N.B., E.M., D.L., A.V.), Marseille, France.

^* To whom correspondence should be addressed. E-mail: dominique.lombardo{at}medecine.univ-mrs.fr.

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.

Methods and 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.

Key words: atherosclerosis • arteries • muscle, smooth

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