title: Smoothelin-B is not a target of matrix metalloproteinase (MMP)-2 in the vasculature of endotoxemic rats.
abstract: Smoothelin-B (SMTL-B) and calponin-1 are important regulators of vascular contraction. SMTL-B contains a calponin-homology domain and is structurally similar to cardiac troponin T. As calponin-1 and troponin T are proteolyzed by intracellular matrix metalloproteinase (MMP)-2 in oxidative stress injury, we hypothesized that SMTL-B is also cleaved by MMP-2 and contributes to lipopolysaccharide (LPS)-induced vascular hypocontractility. Rats received ONO-4817 (an MMP inhibitor) or its vehicle, 2 h prior to being administered lipopolysaccharide (LPS). LPS-induced aorta hypocontractility to potassium chloride or phenylephrine, and reduction of calponin-1 levels, were abolished by ONO-4817 at 6 but not 3 h after LPS. However, the level of SMTL-B was unaltered in LPS aortas and further unaffected by ONO-4817. Despite the importance of SMTL-B in vascular tone, it is not a target of MMP-2 in LPS-induced hypocontractility.
authors.affiliation: a Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: de Souza
authors.forename: Michele
authors.initials: M
authors.lastname: Mazzaron de Castro
authors.forename: Gillian
authors.initials: G
authors.lastname: Goobie
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: da Silva-Santos
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003198:Computer Simulation; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D019446:Endotoxemia / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D003598:Cytoskeletal Proteins; D008070:Lipopolysaccharides; D020778:Matrix Metalloproteinase 2; D008840:Microfilament Proteins; D009124:Muscle Proteins; D000096985:Calponins; C491051:Smtn protein, rat
keywords: aorta; aorte; calponin-1; calponine-1; hypo-contractilité; hypocontractility; inhibiteur des métalloprotéases de la matrice; lipopolysaccharide; matrix metalloproteinase inhibitor; peroxynitrite; protease; protéase; sepsie; sepsis