Anti-angiogenic activity of the mutant Dutch Aβ peptide on human brain microvasular endothelial cells
Daniel Paris, Ghania Ait-Ghezala, Venkatarajan S. Mathura, Nikunj Patel, Amita Quadros, Vincent Laporte, Mike Mullan. Brain Res Mol Brain Res. 2005 May 20;136(1-2):212-30.
Cerebral amyloid angiopathy, the deposition of β-amyloid (Aβ) in the cerebrovasculature, characterizes a rare disorder called hereditary cerebral hemorrhage with amyloidosis-Dutch type (HCHWA-D). A single point mutation of the β-amyloid precursor protein leads to HCHWA-D, resulting in recurrent hemorrhagic stroke at middle age, vascular dementia, and fatal cerebral bleeding.
Wild-type Aβ has been shown to be anti-angiogenic, and both structural and functional cerebromicrovascular abnormalities are associated with Alzheimer's disease. This study found Dutch Aβ to be an even more potent inhibitor of angiogenesis. To better understand the molecular mechanisms that cause the anti-angiogenic activity of Dutch Aβ, researchers profiled genes that were differentially expressed in human brain microvascular endothelial cells exposed to an anti-angiogenic dose of Dutch Aβ. The genes affected by Dutch Aβ were uploaded to the IPA application and network analysis revealed that exposure to Dutch AB dysregulates networks involved in cellular migration, cellular proliferation, angiogenesis, atherosclerosis, and tumorigenesis. |
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