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Isolation and Identification of Vascular Endothelial Cells from Distinct Adipose Depots for Downstream Applications
Published on: June 10, 2022
Obesity-related circulating endothelial extracellular vesicles negatively affect cerebral microvascular cell function
Samuel T Ruzzene1, Vinicius P Garcia1, Auburn R Berry1
1Integrative Vascular Biology Laboratory, Department of Integrative Physiology, University of Colorado Boulder, Boulder, Colorado, United States.
Summary
Endothelial cell-derived extracellular vesicles (EEVs) from obese adults impair brain endothelial cell function. These vesicles reduce nitric oxide production and increase endothelin-1, potentially increasing stroke risk.
Area of Science:
- Cardiovascular Science
- Neuroscience
- Cell Biology
Background:
- Obesity is linked to increased cerebrovascular dysfunction and stroke risk.
- Endothelial cell-derived extracellular vesicles (EEVs) are implicated in intercellular communication and disease pathogenesis.
Purpose of the Study:
- To investigate the in vitro effects of EEVs from obese adults on brain microvascular endothelial cells.
- To assess the impact of EEVs on nitric oxide (NO), endothelin-1 (ET-1), and tissue-type plasminogen activator (t-PA) production.
Main Methods:
- EEVs were isolated from normal weight and obese adults using flow cytometry.
- Human cerebral microvascular endothelial cells (hCMECs) were treated with EEVs.
- NO, ET-1, and t-PA levels were measured, along with endothelial nitric oxide synthase (eNOS) phosphorylation.
Main Results:
- EEVs from obese adults reduced NO production by ~20% in hCMECs.
- EEVs from obese adults increased ET-1 production and expression of its precursors.
- t-PA release was significantly lower in hCMECs treated with EEVs from obese adults.
Conclusions:
- Circulating EEVs from obese individuals may mediate obesity-related cerebrovascular dysfunction.
- EEVs could be a significant factor contributing to increased stroke risk in obesity.
- Targeting EEVs may offer a therapeutic strategy for mitigating obesity-associated vascular complications.
