Trafficking of the membrane type-1 matrix metalloproteinase in ischemia and reperfusion: relation to interstitial membrane type-1 matrix metalloproteinase activity.
Circulation
; 111(9): 1166-74, 2005 Mar 08.
Article
em En
| MEDLINE
| ID: mdl-15723986
ABSTRACT
BACKGROUND:
The matrix metalloproteinases (MMPs) contribute to regional remodeling after prolonged periods of ischemia and reperfusion (I/R), but specific MMP types activated during this process remain poorly understood. A novel class, the membrane-type MMPs (MT-MMPs), has been identified in the myocardium, but activity of these MMP types has not been assessed in vivo, particularly during I/R. METHODS ANDRESULTS:
Pigs (30 kg, n=8) were instrumented with microdialysis catheters to measure MT1-MMP activity in both ischemic and nonischemic (remote) myocardium. A validated MT1-MMP fluorogenic substrate was infused through the microdialysis system, and changes in fluorescence were reflective of MT1-MMP activity at steady state, during ischemia (90 minutes), and during reperfusion (120 minutes). At peak ischemia, MT1-MMP activity was increased by >40% in the ischemic region, with no change in the remote region, which persisted with reperfusion (P<0.05). After I/R, MT1-MMP abundance was increased by >50% (P<0.05). Differential centrifugation revealed that the endosomal fraction (which contains subcellular organelles) within the ischemic myocardium was associated with a >135% increase in MT1-MMP (P<0.05). Furthermore, in an isolated left ventricular myocyte model of I/R, hypoxia (simulated ischemia) induced a >70% increase in MT1-MMP abundance in myocytes, and confocal microscopy revealed MT1-MMP internalization during this time period and reemergence to the membrane with reperfusion.CONCLUSIONS:
These unique results demonstrate that a specific MMP type, MT1-MMP, is increased in abundance and activity with I/R and is likely attributed, at least in part, to changes in intracellular trafficking.
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Base de dados:
MEDLINE
Assunto principal:
Metaloendopeptidases
/
Traumatismo por Reperfusão Miocárdica
/
Isquemia Miocárdica
/
Transporte Proteico
/
Miócitos Cardíacos
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article