金新春教授在J Neurochem杂志上发表署名论文Caveolin-1 mediates tissue plasminogen activator-induced MMP-9 upregulation in cultured brain microvascular endothelial cells.
Abstract:
Hemorrhagic transformation (HT) is the most feared neurovascular complication in thrombolytic therapy for ischemic
stroke (Alberts 1998; Yepes et al. 2003), which occurs as a result of catastrophic failure of the blood-brain barrier (BBB) integrity (Hamann et al. 1996; Simard et al. 2007). Matrix metalloproteinases (MMPs), a family of zinc-binding proteolytic enzymes, play an important role in mediating BBB disruption after cerebral ischemia by degrading the major
structural components (Rosenberg and Mun-Bryce 2004; Rosell and Lo 2008).
Accumulating experimental evidence supports a close association between MMP-9 induction and tPA-associated
HT in ischemic stroke. Human studies indicated that stroke patients with higher pretreatment plasma levels of MMP-9
are more likely to experience cerebral hemorrhagic complications after tPA treatment (Castellanos et al. 2003, 2004; Montaner et al. 2003), and inhibition of MMPs with pharmacologic inhibitors significantly reduces the incidence of tPA-associated hemorrhage and mortality in ischemic stroke animal models (Lapchak et al. 2000; Pfefferkorn and Rosenberg 2003). tPA has been reported to up-regulate and activate MMP-9 (Wang et al. 2003; Cheng et al. 2006); however, the underlying mechanism remains unclear.
