首页> 外文期刊>Microvascular Research: An International Journal >Human postmortem brain-derived cerebrovascular smooth muscle cells express all genes of the classical complement pathway: A potential mechanism for vascular damage in cerebral amyloid angiopathy and Alzheimer's disease.
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Human postmortem brain-derived cerebrovascular smooth muscle cells express all genes of the classical complement pathway: A potential mechanism for vascular damage in cerebral amyloid angiopathy and Alzheimer's disease.

机译:人类死后脑源性脑血管平滑肌细胞表达经典补体途径的所有基因:在脑淀粉样血管病和阿尔茨海默氏病中潜在的血管损伤机制。

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摘要

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 (Abeta) 1-42 increased expression of complement C3 mRNA and increased release of C3 protein. Abeta 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 Abeta 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.
机译:在大多数阿尔茨海默氏病(AD)病例中发现的血管周围淀粉样蛋白沉积,称为脑淀粉样蛋白血管病(CAA),是一种主要的病理特征,在AD脑中的CAA沉积物中已检测到活化的补体片段。在这项研究中,我们首次证明从死后大脑皮层血管中分离出的人脑血管平滑肌细胞(HCSMC)可以表达补体基因C1qB,C1r,C1s,C2,C3,C4,C5,C6,C7的mRNA ,C8和C9是经典补体途径的组成部分。除了C1q和C5外,还证明了这些基因的相应补体蛋白的分泌。特别有意义的是观察到,用聚集的淀粉样蛋白β(Abeta)1-42处理HCSMC可增加补体C3 mRNA的表达并增加C3蛋白的释放。 HCSMC的Abeta处理也增加了C6 mRNA的表达。干扰素-γ诱导补体C1r,C1s,C2和C4的表达和释放。由于HCSMC与脑血管中的Abeta沉积物密切相关,因此补体蛋白的产生可放大淀粉样蛋白在血管周围环境中的促炎作用,从而进一步损害脑血管的完整性。

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