The Serpin Protease-Nexin 1 Is Present in Rat Aortic Smooth Muscle Cells and Is Upregulated in l -NAME Hypertensive Rats
Autor: | Marie-Claude Guillin, Patrick Rossignol, Benjamin Richard, Jean-Baptiste Michel, Marie-Christine Bouton, Martine Jandrot-Perrus, Monique Philippe |
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Rok vydání: | 2003 |
Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Administration Oral Receptors Cell Surface Serpin Biology Muscle Smooth Vascular Amyloid beta-Protein Precursor Thrombin Downregulation and upregulation In vivo Internal medicine Serpin E2 medicine Animals Humans Nitric Oxide Donors Rats Wistar Aorta Cells Cultured Serpins Protease Angiotensin II Heparin Immunohistochemistry Recombinant Proteins In vitro Rats Up-Regulation Protease Nexins NG-Nitroarginine Methyl Ester Endocrinology Biochemistry Cell culture Hypertension Calcium Carrier Proteins Cardiology and Cardiovascular Medicine Cell Division medicine.drug |
Zdroj: | Arteriosclerosis, Thrombosis, and Vascular Biology. 23:142-147 |
ISSN: | 1524-4636 1079-5642 |
DOI: | 10.1161/01.atv.0000047867.98019.2d |
Popis: | 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. |
Databáze: | OpenAIRE |
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