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A Visual Approach for Inducing Dolichoectasia in Mice to Model Large Vessel-Mediated Cerebrovascular Dysfunction
Published on: May 17, 2024
Age-related circulating endothelial extracellular vesicles promote cerebral microvascular cell dysfunction
Auburn R Berry1, Samuel T Ruzzene1, Vinicius P Garcia1
1Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States.
Summary
Endothelial cell-derived extracellular vesicles (EEVs) from older adults increase oxidative stress and impair nitric oxide (NO) production in brain cells. These findings suggest EEVs may contribute to age-related stroke risk.
Area of Science:
- Cardiovascular Science
- Neuroscience
- Aging Research
Background:
- Endothelial cell-derived extracellular vesicles (EEVs) play roles in intercellular communication.
- Aging is associated with increased risk of cerebrovascular diseases, including stroke.
- The specific impact of EEVs from older adults on brain microvascular endothelial cells is not fully understood.
Purpose of the Study:
- To investigate the in vitro effects of EEVs from older adults on brain microvascular endothelial cell function.
- To assess the impact on oxidative stress, inflammation, nitric oxide (NO), endothelin (ET)-1, and tissue-type plasminogen activator (t-PA) release.
Main Methods:
- Isolation and enumeration of circulating EEVs (CD144+) from young and older adults using flow cytometry.
- Treatment of human cerebral microvascular endothelial cells (hCMECs) with EEVs from both age groups.
- Measurement of reactive oxygen species (ROS), antioxidant enzyme expression (catalase, SOD-1), inflammatory markers, NO, ET-1, and t-PA release.
Main Results:
- EEVs from older adults significantly increased ROS production and decreased catalase and SOD-1 expression in hCMECs.
- EEVs from older adults led to reduced phosphorylated eNOS (Ser1177), increased phosphorylated eNOS (Thr495), and lower NO production.
- EEVs from older adults elevated Big ET-1 and ECE expression and ET-1 production, while decreasing t-PA release.
- No significant cellular inflammation was induced by EEVs from older adults.
Conclusions:
- Circulating EEVs from older adults induce oxidative stress and impair endothelial function in brain microvascular cells.
- These EEV-mediated changes in NO and ET-1 balance may contribute to increased cerebrovascular risk with aging.
- EEVs represent a potential mechanistic link between aging and heightened stroke risk.
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