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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:142.)
© 2003 American Heart Association, Inc.

Thrombosis

The Serpin Protease-Nexin 1 Is Present in Rat Aortic Smooth Muscle Cells and Is Upregulated in L-NAME Hypertensive Rats

Marie-Christine Bouton; Benjamin Richard; Patrick Rossignol; Monique Philippe; Marie-Claude Guillin; Jean-Baptiste Michel; Martine Jandrot-Perrus

From Equipe INSERM E9907 and Unité INSERM U460 (P.R., M.P., J.-B.M.), Faculté Xavier Bichat, Paris, France.

Correspondence to Dr Marie-Christine Bouton, Faculté X. Bichat, Equipe INSERM E9907, BP 416, 75870 Paris, Cedex 18, France. E-mail mcbouton{at}bichat.inserm.fr

Objective— Protease-nexin 1 (PN-1) belongs to the serpin superfamily and behaves as a specific thrombin inhibitor in the pericellular environment. Little is known about PN-1 expression and its regulation in the vascular system. In this study, we examined the expression of functionally active PN-1 in vitro in rat aortic smooth muscle cells and in vivo in rat arterial media and its regulation in hypertensive rats.

Methods and Results— The vascular PN-1 formed specific covalent complexes with thrombin involving the catalytic site of the protease, and heparin increased the formation of these complexes. We also demonstrated PN-1 in rat arterial media by immunohistochemical staining. Moreover, we examined in vivo vascular expression of PN-1 in a model of chronic hypertension induced by long-term administration of N^G-nitro-L-arginine methyl ester (L-NAME). Marked increases in PN-1 mRNA (3-fold) and protein (2-fold) were observed after 2 months of hypertension. Increased expression of PN-1 in the vascular wall was associated with an increase in the formation of complexes between radiolabeled-thrombin and PN-1, indicating that PN-1 was functional.

Conclusions— PN-1 may thus participate in the mechanisms that regulate thrombin activity in the vessel wall.

Key Words: protease-nexin 1 • smooth muscle cells • aorta • hypertension • thrombin

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