Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction DOI Creative Commons
Cathrin E. Hansen,

Davide Vacondio,

Lennart van der Molen

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Abstract Aging of the brain vasculature plays a key role in development neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, genomic instability endothelial cells (EC) its potential effect on homeostasis is still largely unclear. We here investigated how aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human ECs an EC-specific Ercc1 knock out (EC-KO) mouse model. In vitro, ERCC1-deficient displayed increased senescence-associated secretory phenotype (SASP) expression, reduced BBB integrity higher sprouting capacities due underlying dysregulation Dll4-Notch pathway. In line, EC-KO mice showed more P21+ cells, augmented expression angiogenic markers concomitant increase number pericytes. Moreover, leakage enhanced cell adhesion molecule accompanied peripheral immune infiltration into brain. These findings were confined white matter, suggesting regional susceptibility. Collectively, our results underline as driver impaired function, migration brain, observed during process.

Language: Английский

Free radicals in Alzheimer’s disease: from pathophysiology to clinical trial results DOI Creative Commons
José Viña, Consuelo Borrás, Cristina Mas‐Bargues

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

Citations

1
Endothelial-Ercc1 DNA repair deficiency provokes blood-brain barrier dysfunction DOI Creative Commons
Cathrin E. Hansen,

Davide Vacondio,

Lennart van der Molen

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 1, 2024

Abstract Aging of the brain vasculature plays a key role in development neurovascular and neurodegenerative diseases, thereby contributing to cognitive impairment. Among other factors, DNA damage strongly promotes cellular aging, however, genomic instability endothelial cells (EC) its potential effect on homeostasis is still largely unclear. We here investigated how aging impacts blood-brain barrier (BBB) function by using excision repair cross complementation group 1 (ERCC1)-deficient human ECs an EC-specific Ercc1 knock out (EC-KO) mouse model. In vitro, ERCC1-deficient displayed increased senescence-associated secretory phenotype (SASP) expression, reduced BBB integrity higher sprouting capacities due underlying dysregulation Dll4-Notch pathway. In line, EC-KO mice showed more P21+ cells, augmented expression angiogenic markers concomitant increase number pericytes. Moreover, leakage enhanced cell adhesion molecule accompanied peripheral immune infiltration into brain. These findings were confined white matter, suggesting regional susceptibility. Collectively, our results underline as driver impaired function, migration brain, observed during process.

Language: Английский

Citations

0