Altered stress hormone levels affect in vivo vascular function in the hAPP23(+/-) overexpressing mouse model of Alzheimer's disease

Jhana O. Hendrickx, Sofie De Moudt, Debby Van Dam, Peter Paul De Deyn, Paul Fransen, Guido R. Y. De Meyer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)
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Abstract

Alzheimer's disease (AD) has long been considered a brain-specific dementia syndrome. However, in recent decades, the occurrence of cardiovascular (CV) disease in the progression of AD has been confirmed by increasing epidemiological evidence. In this study, we conducted an in-depth cardiovascular characterization of a humanized amyloid precursor protein (APP) overexpressing mouse model (hAPP23(+/-)), which overexpresses the Swedish mutation (KM670/671NL). At the age of 6 mo, hAPP23(+/-) mice had a lower survival, lower body weight, and increased corticosterone and VMA levels compared with C57BL/6 littermates. Systolic blood pressure was increased in hAPP23(+/-) animals compared with C57BU6 littermates, but diastolic blood pressure was not statistically different. Pulse pressure remained unchanged but abdominal and carotid pulse-wave velocity (aPWV and cPWV) were increased in hAPP23(+/-) compared with C57BL/6 mice. Echocardiography showed no differences in systolic or diastolic cardiac function. Ex vivo evaluation of vascular function showed decreased adreno receptor dependent vasoconstriction of hAPP23(+/-) aortic segments, although the isobaric biomechanics of the aortic wall were similar to C57BL/6 aortic segments. In conclusion, hAPP23(+/-) mice exhibited high serum corticosterone levels, elevated systolic blood pressure, and increased arterial stiffness in vivo. However, ex vivo aortic stiffness of hAPP23(+/-) aortic segments was not changed and vascular reactivity to alpha(1)-drenoceptor stimulation was attenuated. These findings highlight the need for more frequent assessment of circulating stress hormone levels and PWV measurements in daily clinical practice for people at risk of AD.

NEW & NOTEWORTHY We showed that male amyloid precursor protein (APP) transgenic mice have higher circulating stress hormone levels. As a result, higher systolic blood pressure and pulse-wave velocity were measured in vivo in addition to a smaller alpha-adrenergic receptor-dependent contraction upon ex vivo stimulation with phenylephrine. Our findings highlight the need for more frequent assessment of circulating stress hormone levels and PWV measurements in daily clinical practice for people at risk of Alzheimer's disease.

Original languageEnglish
Pages (from-to)H905-H919
Number of pages15
JournalAMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume321
Issue number5
DOIs
Publication statusPublished - 11-Oct-2021

Keywords

  • alpha-adrenergic receptor-dependent contraction
  • amyloid precursor protein
  • hypercortisolism
  • pulse-wave velocity
  • stress hormone
  • PULSE-WAVE VELOCITY
  • CORTICOTROPIN-RELEASING-FACTOR
  • ANTIHYPERTENSIVE DRUG-THERAPY
  • BLOOD-PRESSURE VARIABILITY
  • ARTERIAL STIFFNESS
  • AMYLOID-BETA
  • PROTEIN
  • MICE
  • DEFICITS
  • AGE

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