Native and oxidised low-density lipoproteins modulate the vasoactive actions of soluble β-amyloid peptides in rat aorta

Christopher Ct Smith (1) , Lee Stanyer , D John Betteridge , Michael B Cooper

1 Medicine

Cerebrovascular accumulation of β-amyloid (Aβ) occurs in aging and Alzheimer's disease (AD). Hypercholesterolaemia, which is associated with raised plasma low-density lipoprotein (LDL), 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 polymerisation leading to Aβ fibrillogenesis, we investigated the influence of low density lipoprotein (LDL) on the vasoactive actions of soluble Aβ peptides. Thus, the actions of Aβ 40 and Aβ 42 in combination with native or oxidised LDL on vasoconstriction to noradrenaline (NA) and vasodilatation to acetylcholine (ACh) were examined in rat aortic rings. LDL, particularly when oxidised, potentiated NA-induced constriction when combined with soluble Aβ 40 and, especially, Aβ 42. Soluble Aβ 40 reduced relaxation induced by ACh but Aβ 42 was ineffective. Native and oxidised LDL also attenuated relaxation. Synergism occurred between oxidised 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 oxidised, modulates the vascular actions of soluble Aβ peptides 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.

Mots clés: Medicine

Christopher Ct Smith, Lee Stanyer, D John Betteridge, Michael B Cooper. Native and oxidised low-density lipoproteins modulate the vasoactive actions of soluble β-amyloid peptides in rat aorta. Clinical Science, 2007, 113 (11), pp.427-434. ⟨10.1042/CS20070082⟩. ⟨hal-00479372⟩