Departments of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.
Departments of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota.
Basic Clin Pharmacol Toxicol. 2020 Aug;127(2):102-110. doi: 10.1111/bcpt.13403. Epub 2020 Mar 23.
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.
脑血管内皮细胞（CECs）是血脑屏障（BBB）和神经血管单元（NVU）的重要组成部分。作为 BBB 的主要细胞类型，CECs 负责严格调节脑实质与外周之间的分子转运。此外，CECs 在神经血管耦联中也起着至关重要的作用，它们有助于根据 NVU 中细胞需求的区域增加来调节脑血流。CEC 功能障碍发生在正常衰老和脑血管疾病期间，导致 BBB 通透性增加和神经血管解耦。这篇 MiniReview 总结了与 CEC 功能障碍相关的分子变化，其中许多变化与已经衰老的细胞相似。一般来说，细胞衰老被定义为一种不可逆的生长停滞，其特征是在 DNA 损伤或其他细胞应激下获得促炎分泌表型。我们讨论了内皮细胞衰老在衰老和心血管疾病中的证据，以及 CEC 衰老如何导致与年龄相关的脑血管功能障碍。
