title: The serpin protease-nexin 1 is present in rat aortic smooth muscle cells and is upregulated in L-NAME hypertensive rats.
abstract: 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.
  
  
  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.
authors.affiliation: Equipe INSERM E9907 and Unité INSERM U460, Faculté Xavier Bichat, Paris, France. mcbouton@bichat.inserm.fr
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Bouton
authors.forename: Benjamin
authors.initials: B
authors.lastname: Richard
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.forename: Monique
authors.initials: M
authors.lastname: Philippe
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Guillin
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Michel
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
mesh_terms: D000284:Administration, Oral; D016564:Amyloid beta-Protein Precursor; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D058255:Protease Nexins; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins / Q000494:pharmacology; D058258:Serpin E2; D015843:Serpins / Q000096:biosynthesis* / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D002352:Carrier Proteins; D020030:Nitric Oxide Donors; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C545486:SERPINE2 protein, human; D058258:Serpin E2; D015843:Serpins; D000804:Angiotensin II; D013917:Thrombin; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester