The serpin protease-nexin 1 is present in rat aortic smooth muscle cells and is upregulated in L-NAME hypertensive rats

Arterioscler Thromb Vasc Biol. 2003 Jan 1;23(1):142-7. doi: 10.1161/01.atv.0000047867.98019.2d.

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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Amyloid beta-Protein Precursor
  • Angiotensin II / pharmacology
  • Animals
  • Aorta / metabolism*
  • Aorta / pathology
  • Calcium / metabolism
  • Carrier Proteins / biosynthesis*
  • Carrier Proteins / immunology
  • Carrier Proteins / pharmacology
  • Carrier Proteins / physiology*
  • Cell Division / drug effects
  • Cells, Cultured
  • Humans
  • Hypertension / chemically induced*
  • Hypertension / metabolism*
  • Immunohistochemistry
  • Male
  • Muscle, Smooth, Vascular / chemistry*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism
  • Muscle, Smooth, Vascular / pathology
  • NG-Nitroarginine Methyl Ester / administration & dosage*
  • Nitric Oxide Donors / pharmacology
  • Protease Nexins
  • Rats
  • Rats, Wistar
  • Receptors, Cell Surface
  • Recombinant Proteins / pharmacology
  • Serpin E2
  • Serpins / biosynthesis*
  • Serpins / immunology
  • Serpins / pharmacology
  • Serpins / physiology*
  • Thrombin / antagonists & inhibitors
  • Thrombin / pharmacology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology*

Substances

  • Amyloid beta-Protein Precursor
  • Carrier Proteins
  • Nitric Oxide Donors
  • Protease Nexins
  • Receptors, Cell Surface
  • Recombinant Proteins
  • SERPINE2 protein, human
  • Serpin E2
  • Serpins
  • Angiotensin II
  • Thrombin
  • Calcium
  • NG-Nitroarginine Methyl Ester