Paris D, Town T, Parker T A, Humphrey J, Mullan M
The Roskamp Institute, University of South Florida, Department of Psychiatry, Tampa 33613, USA.
Neurosci Lett. 1998 Nov 6;256(2):73-6. doi: 10.1016/s0304-3940(98)00764-2.
Abeta peptides are thought to be centrally involved in Alzheimer's disease (AD) pathogenesis, although Abeta's pathophysiological mechanisms remain to be elucidated. We previously showed that soluble beta-amyloid1-40 (Abeta) and Abeta1-42 exhibit vasoactive properties, and are able to promote vasoconstriction in rat aortae induced by an endogenous vasoconstrictor, endothelin-1. It is well established that the APOE epsilon4 allele confers risk for both familial and sporadic AD, as well as for hypertension. We now report that physiologic amounts (10 nM) of specific human recombinant apoE isoforms are vasoactive (E4 > E3, and not E2) in isolated rat aortae. In order to investigate if various apoE isoforms could modulate Abeta vasoactivity, we co-incubated Abeta1-40 with various isoforms of apoE in our tissue bath system. Our results show that, while none of the APOE isoforms are able to affect the maximum constriction induced by Abeta; the apoE E4 isoform synergistically enhances the rate of vasoconstriction induced by Abeta. Our data suggest that apoE may promote hypertension and contribute to AD pathogenesis via enhancement of vasoconstriction, and support a link between hypertension, cerebral amyloid angiopathy and AD.
β-淀粉样肽被认为在阿尔茨海默病（AD）发病机制中起核心作用，尽管β-淀粉样肽的病理生理机制仍有待阐明。我们之前表明，可溶性β-淀粉样蛋白1-40（Aβ）和Aβ1-42具有血管活性，并且能够促进内源性血管收缩剂内皮素-1诱导的大鼠主动脉血管收缩。众所周知，APOEε4等位基因会增加家族性和散发性AD以及高血压的发病风险。我们现在报告，在离体大鼠主动脉中，生理量（10 nM）的特定人类重组载脂蛋白E异构体具有血管活性（E4 > E3，而非E2）。为了研究各种载脂蛋白E异构体是否能调节Aβ的血管活性，我们在组织浴系统中将Aβ1-40与各种载脂蛋白E异构体共同孵育。我们的结果表明，虽然没有一种载脂蛋白E异构体能够影响Aβ诱导的最大收缩；但载脂蛋白E4异构体协同增强了Aβ诱导的血管收缩速率。我们的数据表明，载脂蛋白E可能通过增强血管收缩促进高血压并导致AD发病机制，支持了高血压、脑淀粉样血管病和AD之间的联系。
