Journal
MICROVASCULAR RESEARCH
Volume 75, Issue 3, Pages 411-419Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mvr.2007.10.004
Keywords
vasculature; inflammation; amyloid; toxicity; neurodegeneration; cell culture; gene expression
Categories
Funding
- NIA NIH HHS [R01 AG018345, R01 AG18345] Funding Source: Medline
Ask authors/readers for more resources
Deposition of amyloid around blood vessels, known as cerebral amyloid angiopathy (CAA), is a major pathological feature found in the majority of Alzheimer's disease (AD) cases, and activated complement fragments have been detected on CAA deposits in AD brains. In this study, we demonstrate for the first time that human cerebrovascular smooth muscle cells (HCSMC) isolated from cortical vessels derived from postmortem brains can express mRNAs for complement genes C1qB, C1r, C1s, C2, C3, C4, C5, C6, C7, C8 and C9, the components of the classical complement pathway. Secretion of the corresponding complement proteins for these genes was also demonstrated, except for C1q and C5. Of particular significance was the observation that treatment of HCSMC with aggregated amyloid beta (A beta) 1-42 increased expression of complement C3 mRNA and increased release of C3 protein. A beta treatment of HCSMC also increased expression of C6 mRNA. Interferon-gamma induced expression and release of complement C1r, C1s, C2 and C4. As HCSMC are closely associated with A beta deposits in vessels in the brain, their production of complement proteins could amplify the proinflammatory effects of amyloid in the perivascular environment, further compromising brain vascular integrity. (c) 2007 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available