Chronic cerebral hypoperfusion induces venous dysfunction via EPAS1 regulation in mice.

ABSTRACT: Vascular dementia is the second most common form of dementia. Yet, the mechanisms by which cerebrovascular damage progresses are insufficiently understood. Here, we create bilateral common carotid artery stenosis in mice, which effectively impairs blood flow to the brain, a major cause of the disease. Through imaging and single-cell transcriptomics of the mouse cortex, we uncover that blood vessel venous cells undergo maladaptive structural changes associated with increased Epas1 expression and activation of developmental angiogenic pathways. In a human cell model comparing arterial and venous cells, we observe that low-oxygen condition leads to sustained EPAS1 signaling specifically in venous cells. EPAS1 inhibition reduces cerebrovascular abnormalities, microglial activation, and improve

SUBMITTER: Wazny VK 

PROVIDER: S-EPMC12238411 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature