Dopamine D4 receptor protected against hyperglycemia-induced endothelial dysfunction via PI3K /eNOS pathway
He Wang1, Yonggang Yao2, Juncheng Liu3
1Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Henan, PR China; Department of Cardiology, The First Affiliated Hospital of Henan University of Chinese Medicine, Henan, PR China.
Biochemical and Biophysical Research Communications
|August 27, 2019
Summary
Dopamine D4 receptors protect against high glucose-induced endothelial damage in diabetes. Activating these receptors via the PI3K/eNOS pathway offers a potential new treatment for diabetic vascular complications.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Pharmacology
Background:
- Diabetic vascular complications are linked to hyperglycemia-induced endothelial dysfunction.
- Dopamine receptors are recognized for their protective role in diabetes, but their specific effect on endothelial damage is unclear.
Purpose of the Study:
- To investigate the protective role of dopamine D4 receptors against hyperglycemia-induced endothelial damage.
- To elucidate the underlying molecular mechanisms involving the PI3K/eNOS pathway.
Main Methods:
- Established a human umbilical vein endothelial cell (HUVEC) model of hyperglycemia.
- Utilized MTT and lactate dehydrogenase assays to assess cell viability and damage.
- Administered a D4 receptor agonist (PD168077) and inhibitors for PI3K and eNOS.
- Examined D4 receptor expression in streptozotocin-induced diabetic rat models.
Main Results:
- High glucose reduced HUVEC viability and downregulated D4 receptor expression.
- PD168077 treatment significantly improved cell viability and reduced apoptosis.
- Inhibition of PI3K/eNOS pathways abolished the protective effects of D4 receptor activation.
- D4 receptor expression was decreased in diabetic rat endothelium, and its activation reversed vasodilation impairment.
Conclusions:
- Dopamine D4 receptor activation protects against hyperglycemia-induced endothelial dysfunction.
- This protection is mediated through the PI3K/eNOS signaling pathway.
- Dopamine D4 receptors represent a potential therapeutic target for diabetic vascular complications.
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