Premium
Matrix metalloproteinase (MMP)‐2 proteolysis of calponin contributes to vascular hypocontractility in endotoxemic rats
Author(s) -
Castro Michele Mazzaron,
Cena Jonathan,
Walsh Michael P.,
Schulz Richard
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.819.2
Increased MMP‐2 activity in aorta from lipopolysaccharide (LPS) treated rats contributes to vascular hypocontractility. Calponin is a 34 kDa contractile protein which regulates vascular smooth muscle tone. It is structurally similar to troponin I, a cardiac myocyte contractile protein which is cleaved by MMP‐2 in myocardial oxidative stress injuries. Calponin may be an intracellular target of MMP‐2 in vascular smooth muscle which contributes to LPS‐induced vascular dysfunction. Rats were given either a non‐lethal dose of LPS (4 mg/kg, i.p.) or vehicle (Control). After 30 min some rats were given doxycycline (Doxy), an MMP inhibitor (4 mg/kg, i.p.). At 6 h, plasma NO x − levels were 8±3 (Control), 141±75 (LPS) and 126±87 μM (LPS+Doxy). LPS enhanced MMP‐2 S‐glutathiolation in aorta which was reversed by dithiothreitol. This was accompanied by a 2.4 fold loss of calponin in LPS vs. Control aorta which was prevented by Doxy. Immunoblot analysis for MMP‐2 of anti‐calponin, but not IgG 1 immunoprecipitates, showed 72 kDa MMP‐2 in Control and LPS aorta. Confocal microscopy revealed that MMP‐2 co‐localizes with calponin in the aortic media layer. Doxycycline (100 μM) also protected against interleukin‐1β‐induced loss of tone and calponin levels in isolated aorta. Calponin may be a proteolytic target of MMP‐2 in vascular smooth muscle thus contributing to LPS‐induced vascular hypocontractility. Grant support from CIHR.