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Sirt6 mRNA-incorporated endothelial microparticles (EMPs) attenuates DM patient-derived EMP-induced endothelial
Tong Jing1, Kuang Ya-Shu1, Wang Xue-Jun1
1Department of Cardiology, Shanghai Tongji Hospital, Tongji University, Shanghai, China.
Background:
Endothelial microparticles (EMPs) are small vesicles released by endothelial cells (ECs); they are considered biomarkers for endothelial dysfunction and therapeutic targets in diabetes-related vascular disease. Sirtuins have also been shown to play important roles in diabetes by regulating endothelial dysfunction. However, the effect of sirtuin-incorporated EMPs on their parental ECs remains unknown.
Aim:
The present study aims to investigate the diagnostic value of EMPs in diabetes and detect the protective effects of sirtuin 6 (Sirt6) mRNA -incorporated EMPs on endothelial dysfunction.
Methods:
EMPs were prepared from cultured HUVECs and venous blood from patients with diabetes (n=10) and from healthy volunteers (n=6) after sequential centrifugation. Adv-Sirt6 or Sirt6 siRNA was used to alter Sirt6 expression. EC angiogenesis, inflammatory phenotypes, nitric oxide (NO) formation and eNOS phosphorylation were used to evaluate endothelial dysfunction.
Results:
The levels of EMPs in diabetic patients and high glucose-cultured HUVECs are high, whereas Sirt6 expression in plasma and EMPs is low. EMPs generated from diabetic patients or high glucose-cultured HUVECs increase inflammatory chemokine release and blunt EC angiogenesis. Furthermore, EMPs enriched with Sirt6 mRNA induces EC angiogenesis, increases eNOS phosphorylation and impedes inflammatory chemokine release. Inhibition of Sirt6 mRNA expression in EMPs by siRNA hinders angiogenesis and eNOS phosphorylation but increases cellular inflammation.
Conclusion:
The Sirt6 mRNA-carrying EMPs may ameliorate endothelial dysfunction in diabetic patients.
Insights
Endothelial microparticles (EMPs) from diabetic patients show low Sirt6. EMPs carrying Sirt6 mRNA protect against endothelial dysfunction by promoting angiogenesis and nitric oxide formation.
Area of Science:
- Cardiovascular Biology
- Metabolic Disease Research
- Cellular Vesicle Biology
Background:
- Endothelial microparticles (EMPs) are biomarkers for endothelial dysfunction and therapeutic targets in diabetic vascular disease.
- Sirtuins regulate endothelial dysfunction in diabetes, but their role within EMPs is unknown.
Purpose of the Study:
- Investigate the diagnostic value of EMPs in diabetes.
- Determine the protective effects of Sirtuin 6 (Sirt6) mRNA-incorporated EMPs on endothelial dysfunction.
Main Methods:
- Prepared EMPs from cultured HUVECs and blood of diabetic patients and healthy volunteers.
- Utilized Adv-Sirt6 and Sirt6 siRNA to modulate Sirt6 expression.
- Assessed endothelial dysfunction via angiogenesis, inflammatory markers, nitric oxide (NO) production, and eNOS phosphorylation.
Main Results:
- Elevated EMP levels and low Sirt6 expression were observed in diabetic patients and high glucose conditions.
- Diabetic EMPs impaired EC angiogenesis and increased inflammation.
- Sirt6 mRNA-enriched EMPs promoted EC angiogenesis, increased eNOS phosphorylation, and reduced inflammation.
Conclusions:
- Sirt6 mRNA-carrying EMPs show potential to ameliorate endothelial dysfunction in diabetic patients.
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