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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1161.)
© 2005 American Heart Association, Inc.

Vascular Biology

Autocrine and Paracrine Transcriptional Regulation of Type IIA Secretory Phospholipase A2 Gene in Vascular Smooth Muscle Cells

Amandine Jaulmes; Brigitte Janvier; Marise Andreani; Michel Raymondjean

From UMR Physiologie et Physiopathologie, Université Pierre et Marie Curie, Paris, France.

Correspondence to Michel Raymondjean, UMR Physiologie et Physiopathologie, Université Pierre et Marie Curie, Case courrier 256, Bâtiment A, 5^ème étage, 7 quai St Bernard, 75252 Paris cedex 05, France. E-mail michel.raymondjean{at}snv.jussieu.fr

Objective— The inflammation that occurs during the development of atherosclerosis is characterized by a massive release of sPLA2-IIA (group IIA secretory phospholipase A2) from vascular smooth muscle cells (VSMCs). We have investigated the autocrine function of sPLA2-IIA in rat aortic and human VSMCs.

Methods and Results— We found that the transcription of the endogenous sPLA2-IIA gene increased by adding a cell supernatant containing human sPLA2-IIA proteins. We show that this effect was independent of the sPLA2 activity using sPLA2-IIA proteins lacking enzyme activity. Transient transfections with various sPLA2-IIA rat promoter-luciferase constructs demonstrated that the C/EBP, NK-B, and Ets transcription factors are involved in the increase in sPLA2-IIA gene transcription. We also found the M-type sPLA2 receptor mRNA in VSMCs, and we showed that the sPLA2-luciferase reporter gene was induced by the specific agonist of the sPLA2 receptor, aminophenylmannopyranoside (APMP), and that this induction was mediated by the same transcription factor-binding sites. Finally, we used a sPLA2-IIA mutant unable to bind heparan-sulfate proteoglycans to show that the binding of wild-type sPLA2-IIA to proteoglycans is essential for the induction of an autocrine loop.

Conclusions— We have thus identified new autocrine and paracrine pathways activating sPLA2-IIA gene expression in rat and human VSMCs.

A cell supernatant containing human sPLA2-IIA proteins increases the transcription of the sPLA2-IIA gene in rat and human VSMCs. This effect, independent of the sPLA2 catalytic activity, could involve a sPLA2 receptor and heparan sulfate proteoglycans binding. We thus describe a new autocrine role of sPLA2-IIA in VSMCs.

Key Words: atherosclerosis • autocrine/paracrine effects • type IIA sPLA2 • vascular smooth muscle cells

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