Matrix metalloproteinases as drug targets in ischemia/reperfusion injury

Deficient blood supply (ischemia) is a common consequence of some surgical procedures and certain pathologies. Once blood circulation is reestablished (reperfusion), a complex series of events results in recruitment of inflammatory cells, rearrangement of the extracellular matrix and induction of cell death, which lead to organ dysfunction. Although ischemia/reperfusion (I/R) injury is an important cause of death, there is no effective therapy targeting the molecular mechanism of disease progression. Matrix metalloproteinases (MMPs), which are important regulators of many cellular activities, have a central role in disease progression after I/R injury, as suggested by numerous studies using MMP inhibitors or MMP-deficient mice. Here, we review the involvement of MMP activity in the various processes following I/R injury and the therapeutic potential of MMP inhibition.Deficient blood supply (ischemia) is a common consequence of some surgical procedures and certain pathologies. Once blood circulation is reestablished (reperfusion), a complex series of events results in recruitment of inflammatory cells, rearrangement of the extracellular matrix and induction of cell death, which lead to organ dysfunction. Although ischemia/reperfusion (I/R) injury is an important cause of death, there is no effective therapy targeting the molecular mechanism of disease progression. Matrix metalloproteinases (MMPs), which are important regulators of many cellular activities, have a central role in disease progression after I/R injury, as suggested by numerous studies using MMP inhibitors or MMP-deficient mice. Here, we review the involvement of MMP activity in the various processes following I/R injury and the therapeutic potential of MMP inhibition.A