Unknown

Dataset Information

0

Endothelium-specific deletion of amyloid-β precursor protein exacerbates endothelial dysfunction induced by aging.


ABSTRACT: 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 endothelium-specific 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.

SUBMITTER: d'Uscio LV 

PROVIDER: S-EPMC8386539 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC6168907 | biostudies-literature
| S-EPMC10870664 | biostudies-literature
| S-EPMC3500044 | biostudies-literature
| S-EPMC3962632 | biostudies-literature
| S-EPMC3000992 | biostudies-literature
| S-EPMC2597474 | biostudies-literature
| S-EPMC5647246 | biostudies-literature
| S-EPMC7699411 | biostudies-literature
| S-EPMC3972325 | biostudies-literature
| S-EPMC6513189 | biostudies-literature