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Article dans une revue

Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease

Abstract :

The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-β (Aβ) deposits and neurofibrillary tangles, cerebrovascular dysfunction is increasingly recognized as fundamental to the pathogenesis of AD. Using an experimental model of limb ischemia in transgenic APPPS1 mice, a model of AD (AD mice), we showed that microvascular impairment also extends to the peripheral vasculature in AD. At D70 following femoral ligation, we evidenced a significant decrease in cutaneous blood flow (- 29%, P < 0.001), collateral recruitment (- 24%, P < 0.001), capillary density (- 22%; P < 0.01) and arteriole density (- 28%; P < 0.05) in hind limbs of AD mice compared to control WT littermates. The reactivity of large arteries was not affected in AD mice, as confirmed by unaltered size, and vasoactive responses to pharmacological stimuli of the femoral artery. We identified blood as the only source of Aβ in the hind limb; thus, circulating Aβ is likely responsible for the impairment of peripheral vasculature repair mechanisms. The levels of the majority of pro-angiogenic mediators were not significantly modified in AD mice compared to WT mice, except for TGF-β1 and PlGF-2, both of which are involved in vessel stabilization and decreased in AD mice (P = 0.025 and 0.019, respectively). Importantly, endothelin-1 levels were significantly increased, while those of nitric oxide were decreased in the hind limb of AD mice (P < 0.05). Our results suggest that vascular dysfunction is a systemic disorder in AD mice. Assessment of peripheral vascular function may therefore provide additional tools for early diagnosis and management of AD.

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Article dans une revue
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https://hal.univ-angers.fr/hal-02616782
Contributeur : Okina Université d'Angers <>
Soumis le : dimanche 24 mai 2020 - 23:35:12
Dernière modification le : samedi 19 septembre 2020 - 03:47:32

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Philippe Bonnin, Nathalie Kubis, Daniel Henrion, Jean-Sébastien Silvestre, Bernard Lévy, et al.. Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease. Angiogenesis, 2018, 21 (3), pp.557-569. ⟨10.1007/s10456-018-9608-7⟩. ⟨hal-02616782⟩

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