Cerebrovascular accumulation of Aβ (β-amyloid) occurs in aging and AD (Alzheimer's disease). Hypercholesterolaemia, which is associated with raised plasma LDL (low-density lipoprotein), may predispose to AD. Soluble Aβ is found in the circulation and enhances vasoconstriction. Under conditions that may favour the formation of short Aβ oligomers, as opposed to more severe polymerization leading to Aβ fibrillogenesis, we investigated the influence of LDLs on the vasoactive actions of soluble Aβ. Thus the actions of Aβ40 and Aβ42 in combination with native or oxidized LDL on vasoconstriction to NA (noradrenaline) and vasodilatation to ACh (acetylcholine) were examined in rat aortic rings. LDL, particularly when oxidized, potentiated NA-induced constriction when combined with soluble Aβ40 and, especially, Aβ42. Soluble Aβ40 reduced relaxation induced by ACh, but Aβ42 was ineffective. Native and oxidized LDL also attenuated relaxation. Synergism occurred between oxidized LDL and Aβ with respect to ACh-induced relaxation, but not between native LDL and Aβ. We have shown for the first time that, under conditions that may result in Aβ oligomer formation, LDL, particularly when oxidized, modulates the vascular actions of soluble Aβ to extents greater than those reported previously for fibrillar Aβ preparations. Mechanisms whereby a treatable condition, namely hypercholesterolaemia, might contribute to the development of the cerebrovascular component of AD are indicated.
Native and oxidized low-density lipoproteins modulate the vasoactive actions of soluble β-amyloid peptides in rat aorta
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Christopher C. T. Smith, Lee Stanyer, D. John Betteridge, Michael B. Cooper; Native and oxidized low-density lipoproteins modulate the vasoactive actions of soluble β-amyloid peptides in rat aorta. Clin Sci (Lond) 1 December 2007; 113 (11): 427–434. doi: https://doi.org/10.1042/CS20070082
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