Arteriosclerosis, thrombosis, and vascular biology, 2012-03, Vol.32 (3), p.662-668
2012
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- Autor(en) / Beteiligte
- Titel
- Matrix metalloproteinase-2 proteolysis of calponin-1 contributes to vascular hypocontractility in endotoxemic rats
- Ist Teil von
- Arteriosclerosis, thrombosis, and vascular biology, 2012-03, Vol.32 (3), p.662-668
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2012
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Matrix metalloproteinase (MMP)-2 is activated in aorta during endotoxemia and plays a role in the hypocontractility to vasoconstrictors. Calponin-1 is a regulator of vascular smooth muscle tone with similarities to troponin, a cardiac myocyte protein that is cleaved by MMP-2 in myocardial oxidative stress injuries. We hypothesized that calponin-1 may be proteolyzed by MMP-2 in endotoxemia-induced vascular hypocontractility. Rats were given a nonlethal dose of bacterial lipopolysaccharide (LPS) or vehicle. Some rats were given the MMP inhibitors ONO-4817 or doxycycline. Six hours later, plasma nitrate+nitrite increased >15-fold in LPS-treated rats, an effect unchanged by doxycycline. Both ONO-4817 and doxycycline prevented LPS-induced aortic hypocontractility to phenylephrine. LPS activated MMP-2 in the aorta by S-glutathiolation. Calponin-1 levels decreased by 25% in endotoxemic aortae, which was prevented by doxycycline. Calponin-1 and MMP-2 coimmunoprecipitated and both exhibited uniform cytosolic staining in medial vascular smooth muscle cells. In vitro incubation of calponin-1 with MMP-2 led to calponin-1 degradation and appearance of its cleavage product. Calponin-1 is a target of MMP-2, which contributes to endotoxemia-induced vascular hypocontractility.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1079-5642eISSN: 1524-4636DOI: 10.1161/ATVBAHA.111.242685Titel-ID: cdi_pubmed_primary_22199370
- Format
- –
- Schlagworte
- Animals, Aorta - enzymology, Aorta - physiopathology, Calcium-Binding Proteins - metabolism, Calponins, Disease Models, Animal, Dose-Response Relationship, Drug, Doxycycline - pharmacology, Endotoxemia - chemically induced, Endotoxemia - enzymology, Endotoxemia - physiopathology, Glutathione - metabolism, Immunoprecipitation, Lipopolysaccharides, Male, Matrix Metalloproteinase 2 - metabolism, Matrix Metalloproteinase Inhibitors, Microfilament Proteins - metabolism, Muscle, Smooth, Vascular - drug effects, Muscle, Smooth, Vascular - enzymology, Muscle, Smooth, Vascular - physiopathology, Phenyl Ethers - pharmacology, Protease Inhibitors - pharmacology, Rats, Rats, Sprague-Dawley, Vasoconstriction - drug effects, Vasoconstrictor Agents - pharmacology