Toxicity of Dutch (E22Q) and Flemish (A21G) mutant amyloid beta proteins to human cerebral microvessel and aortic smooth muscle cells

Citation
Zz. Wang et al., Toxicity of Dutch (E22Q) and Flemish (A21G) mutant amyloid beta proteins to human cerebral microvessel and aortic smooth muscle cells, STROKE, 31(2), 2000, pp. 534-538
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurology,"Cardiovascular & Hematology Research
Journal title
STROKE
ISSN journal
0039-2499 → ACNP
Volume
31
Issue
2
Year of publication
2000
Pages
534 - 538
Database
ISI
SICI code
0039-2499(200002)31:2<534:TOD(AF>2.0.ZU;2-7
Abstract
Background and Purpose-Cerebral amyloid angiopathy (CAA) is characterized b y the deposition of amyloid beta protein (A beta) in cortical and leptomeni ngeal vessels of patients with Alzheimer's disease and hereditary cerebral hemorrhage with amyloidosis, Dutch type. Smooth muscle cells (SMC) from cer ebral microvessels (MV) are of particular interest as a site of AP-related injury because CAA is much more pronounced in the tunica media of cortical arterioles than meningeal arteries. Patients carrying point mutations at re sidues 22 (E22Q) and 21 (E21Q) of A beta show severe CAA with various degre es of brain parenchymal A beta deposition. The purpose of this study was to investigate the effects of 2 mutant E22Q- and A21G-A beta peptides on MV a nd aortic SMC. Methods-SMC were isolated from human cerebral MV and aorta, Cell morphology , viability, and proliferation as parameters of A beta toxicity were invest igated after 3 days of peptide treatment by trypan blue exclusion and [H-3] thymidine incorporation. Results-E22Q-A beta induced significant decreased cellular proliferation an d viability, as well as obvious degeneration of both MV and aortic SMC, A21 G-A beta and wild-type A beta did not cause significant toxicity, as judged by cell morphology, viability, or cell proliferation, on either type of SM C. Conclusions-E22Q-A beta induced greater toxicity in all parameters than A21 G-A beta and wild-type A beta with respect to both MV and aortic SMC, A21G- A beta did not show a significant toxic effect on MV and aortic SMC, This d ifferential effect may be linked to cell type-specific processing and metab olism of mutant forms of AP, Mutations in amyloid precursor protein may lea d to CAA by different pathogenetic mechanisms or share an unknown property that distinguishes them from wild-type A beta.