Basic Clin Pharmacol Toxicol. 2020 Mar 11.
Implicating endothelial cell senescence to dysfunction in the ageing and diseased brain.
Graves SI1, Baker DJ1,2.
1 Departments of Biochemistry and Molecular Biology, Mayo Clinic, 200 1st ST SW, Rochester, MN, 55905, United States.
2 Departments of Pediatric and Adolescent Medicine, Mayo Clinic, 200 1st ST SW, Rochester, MN, 55905, United States. baker.darren@mayo.edu
Abstract
Cerebrovascular endothelial cells (CECs) are integral components of both the blood brain barrier (BBB) and the neurovascular unit (NVU). As the primary cell type of the BBB, CECs are responsible for the tight regulation of molecular transport between the brain parenchyma and the periphery. Additionally, CECs are essential in neurovascular coupling where they help regulate cerebral blood flow in response to regional increases in cellular demand in the NVU. CEC dysfunction occurs during both normative ageing and in cerebrovascular disease, which leads to increased BBB permeability and neurovascular uncoupling. This MiniReview compiles what is known about the molecular changes underlying CEC dysfunction, many of which are reminiscent of cells that have become senescent. In general, cellular senescence is defined as an irreversible growth arrest characterized by the acquisition of a pro-inflammatory secretory phenotype in response to DNA damage or other cellular stresses. We discuss evidence for endothelial cell senescence in ageing and cardiovascular disease, and how CEC senescence may contribute to age-related cerebrovascular dysfunction.
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