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Isolation and Identification of Vascular Endothelial Cells from Distinct Adipose Depots for Downstream Applications
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Endothelial Cell CD36 Reduces Atherosclerosis and Controls Systemic Metabolism
Umar R Rekhi1, Mohamed Omar1, Maria Alexiou1
1Department of Dentistry, University of Alberta, Edmonton, AB, Canada.
Frontiers in Cardiovascular Medicine
|December 10, 2021
Summary
Endothelial cell CD36 plays a key role in fatty acid uptake and metabolism, influencing obesity, insulin resistance, and atherosclerosis. Removing it improves glucose clearance and impacts energy expenditure and disease development differently in males and females.
Area of Science:
- Metabolic disease research
- Cardiovascular science
- Endothelial cell biology
Background:
- High-fat diets promote obesity, insulin resistance, and atherosclerosis via tissue dysregulation.
- Endothelial cell (EC) dysfunction is central to atherosclerosis and insulin resistance.
- CD36 mediates fatty acid uptake and may contribute to EC dysfunction.
Purpose of the Study:
- Investigate the role of endothelial cell CD36 in systemic metabolism and atherosclerosis.
- Determine if targeting EC CD36 can offer novel therapeutic strategies for metabolic diseases.
Main Methods:
- Generated endothelial cell-specific CD36 knockout mice (CD36°) using cre-lox technology (Tie2e cre).
- Studied mice on various diets and crossed them with low-density lipoprotein receptor (LDLR) knockout mice for atherosclerosis assessment.
- Utilized indirect calorimetry to measure energy expenditure and substrate utilization.
Main Results:
- EC CD36 knockout mice exhibited altered fatty acid uptake, increased glucose clearance, and sex-specific changes in metabolism.
- Male EC CD36 knockout mice showed increased carbohydrate utilization and decreased energy expenditure.
- Female EC CD36 knockout/LDLR knockout mice displayed reduced atherosclerosis.
Conclusions:
- Endothelial cell CD36 plays a significant role in systemic metabolism and fatty acid uptake.
- Targeting EC CD36 presents a potential therapeutic avenue for metabolic disorders.
- The study highlights sex-specific effects of EC CD36 on atherosclerosis and energy substrate utilization.
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