Peripheral post-ischemic vascular repair is impaired in a murine model of Alzheimer's disease.
Angiogenesis
; 21(3): 557-569, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-29516292
ABSTRACT
The pathophysiology of sporadic Alzheimer's disease (AD) remains uncertain. Along with brain amyloid-ß (Aß) 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 Aß in the hind limb; thus, circulating Aß 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-ß1 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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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doenças Vasculares Periféricas
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Doença de Alzheimer
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Membro Posterior
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Isquemia
Tipo de estudo:
Prognostic_studies
/
Screening_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Angiogenesis
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
França