TY - JOUR
T1 - Endothelium-specific deletion of amyloid-β precursor protein exacerbates endothelial dysfunction induced by aging
AU - d'Uscio, Livius V.
AU - Katusic, Zvonimir S.
N1 - Publisher Copyright:
© 2021 d'Uscio and Katusic. All Rights Reserved.
PY - 2021
Y1 - 2021
N2 - The physiological function of amyloid precursor protein (APP) in the control of endothelial function during aging is unclear. Aortas of young (4-6 months old) and aged (23-26 months old) wild-type (WT) and endotheliumspecific APP-deficient (eAPP-/-) mice were used to study aging-induced changes in vascular phenotype. Unexpectedly, aging significantly increased protein expression of APP in aortas of WT mice but not in aortas of eAPP-/- mice thereby demonstrating selective upregulation APP expression in vascular endothelium of aged aortas. Most notably, endothelial dysfunction (impairment of endothelium-dependent relaxations) induced by aging was significantly exacerbated in aged eAPP-/- mice aortas as compared to age-matched WT mice. Consistent with this observations, endothelial nitric oxide synthase (eNOS) protein expression was significantly decreased in aged eAPP-/- mice as compared to age matched WT mice. In addition, protein expression of cyclooxygenase 2 and release of prostaglandins were significantly increased in both aged WT and eAPP-/- mice. Notably, treatment with cyclooxygenase inhibitor, indomethacin, normalized endothelium-dependent relaxations in aged WT mice, but not in aged eAPP-/- mice. In aggregate, our findings support the concept that aging-induced upregulation of APP in vascular endothelium is an adaptive response designed to protect and preserve expression and function of eNOS.
AB - The physiological function of amyloid precursor protein (APP) in the control of endothelial function during aging is unclear. Aortas of young (4-6 months old) and aged (23-26 months old) wild-type (WT) and endotheliumspecific APP-deficient (eAPP-/-) mice were used to study aging-induced changes in vascular phenotype. Unexpectedly, aging significantly increased protein expression of APP in aortas of WT mice but not in aortas of eAPP-/- mice thereby demonstrating selective upregulation APP expression in vascular endothelium of aged aortas. Most notably, endothelial dysfunction (impairment of endothelium-dependent relaxations) induced by aging was significantly exacerbated in aged eAPP-/- mice aortas as compared to age-matched WT mice. Consistent with this observations, endothelial nitric oxide synthase (eNOS) protein expression was significantly decreased in aged eAPP-/- mice as compared to age matched WT mice. In addition, protein expression of cyclooxygenase 2 and release of prostaglandins were significantly increased in both aged WT and eAPP-/- mice. Notably, treatment with cyclooxygenase inhibitor, indomethacin, normalized endothelium-dependent relaxations in aged WT mice, but not in aged eAPP-/- mice. In aggregate, our findings support the concept that aging-induced upregulation of APP in vascular endothelium is an adaptive response designed to protect and preserve expression and function of eNOS.
KW - aging
KW - amyloid precursor protein
KW - endothelial nitric oxide synthase
KW - endothelium
KW - prostaglandins
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U2 - 10.18632/aging.203401
DO - 10.18632/aging.203401
M3 - Article
C2 - 34382945
AN - SCOPUS:85113298907
SN - 1945-4589
VL - 13
SP - 19165
EP - 19185
JO - Aging
JF - Aging
IS - 15
ER -