| First Author | Hendrickx JO | Year | 2021 |
| Journal | Am J Physiol Heart Circ Physiol | Volume | 321 |
| Issue | 5 | Pages | H905-H919 |
| PubMed ID | 34506227 | Mgi Jnum | J:311362 |
| Mgi Id | MGI:6762366 | Doi | 10.1152/ajpheart.00254.2021 |
| Citation | Hendrickx JO, et al. (2021) Altered stress hormone levels affect in vivo vascular function in the hAPP23(+/-) overexpressing mouse model of Alzheimer's disease. Am J Physiol Heart Circ Physiol |
| abstractText | 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 APP overexpressing mouse model (hAPP23(+/-)), which overexpresses the Swedish mutation (KM670/671NL). At the age of 6 months, hAPP23(+/-) mice had a lower survival, lower body weight and increased corticosterone and VMA levels compared to C57BL/6 littermates. Systolic blood pressure was increased in hAPP23(+/-) animals compared to C57BL/6 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 to 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 alpha1-adrenoceptor 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. |
