Lee Jin-Moo, Yin Ke-Jie, Hsin Idar, Chen Shawei, Fryer John D, Holtzman David M, Hsu Chung Y, Xu Jian
Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, 660 S. Euclid Avenue, Campus Box 8111, St. Louis, MO, USA.
Ann Neurol. 2003 Sep;54(3):379-82. doi: 10.1002/ana.10671.
We examined the potential role of the extra-cellular matrix-degrading enzyme, matrix metalloproteinase-9 (MMP-9), in the pathogenesis of cerebral amyloid angiopathy (CAA)-induced spontaneous hemorrhage. The amyloid-beta peptide (Abeta) induced the synthesis, release and activation of MMP-9 in murine cerebral endothelial cells, resulting in increased extracellular matrix degradation. Furthermore, extensive MMP-9 immunoreactivity was observed in CAA-vessels with evidence of microhemorrhage in aged APPsw transgenic mice, but not detected in aged wild type or young APPsw mice. These results suggest that increased vascular MMP-9 expression, stimulated by Abeta, may play a role in the pathogenesis of spontaneous intracerebral hemorrhage in patients with CAA.
我们研究了细胞外基质降解酶基质金属蛋白酶-9（MMP-9）在脑淀粉样血管病（CAA）所致自发性脑出血发病机制中的潜在作用。淀粉样β肽（Aβ）可诱导小鼠脑内皮细胞中MMP-9的合成、释放及激活，导致细胞外基质降解增加。此外，在老年APPsw转基因小鼠的CAA血管中观察到广泛的MMP-9免疫反应性，且有微出血证据，但在老年野生型或年轻APPsw小鼠中未检测到。这些结果表明，由Aβ刺激引起的血管MMP-9表达增加可能在CAA患者自发性脑出血的发病机制中起作用。
