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Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway

Abstract

Platelet microparticles (PMPs) are closely associated with diabetic macrovascular complications. The present study aimed to investigate the effects of PMPs in diabetes on aortic vascular endothelial injury and to explore the underlying mechanisms. Peritoneal injection of streptozotocin was used to generate a diabetic rat model in vivo, and human umbilical vein endothelial cells (HUVECs) treated with PMPs were used in vitro. PMP levels in the circulation and aorta tissues were time-dependently increased in streptozotocin-induced diabetic rats at weeks 4, 8, and 12 (P < 0.05). Aspirin significantly inhibited the PMP levels at each time point (P < 0.05). In diabetic rats, the endothelial nitric oxide levels were decreased significantly combined with increased endothelial permeability. PMPs were internalized by HUVECs and primarily accumulated around the nuclei. PMPs inhibited endothelial nitric oxide levels to about 50% and caused approximately twofold increase in reactive oxygen species production. Furthermore, PMPs significantly decreased the endothelial glycocalyx area and expression levels of glypican-1 and occludin (P < 0.05). Interestingly, the PMP-induced endothelial injuries were prevented by raptor siRNA and rapamycin. In conclusion, increased PMPs levels contribute to aortic vascular endothelial injuries in diabetes through activating the mTORC1 pathway.

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Acknowledgements

The authors would like to thank Dr. Ze-hui Hong for his kind assistance during the animal experiments. This work was supported by the National Natural Science Foundation of China (81470957), the Jiangsu Province Six Talent Peaks Project (2015-WSN-002), the Project for Jiangsu Provincial Medical Talent (ZDRCA2016077), the Fundamental Research Funds for the Central Universities (KYCX18-0182, KYCX17-0169, KYZZ15-0061), the Jiangsu Province Ordinary University Graduate Research Innovation Project (SJZZ16-004), and the Jiangsu Province Social Development Project (BE2018744).

Author contributions

G-hW performed the in vivo and in vitro experiments, analyzed data, and wrote the manuscript. K-lM designed the research, analyzed data, and wrote the manuscript. YZ performed the in vivo experiments and analyzed data. Z-bH, LL, JL, P-pC and C-cL performed the in vivo and in vitro experiments. X-zR and B-cL analyzed and interpreted the data. All authors read and approved the final manuscript.

Author information

Correspondence to Kun-ling Ma.

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The authors declare no competing interests.

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Keywords

  • platelet microparticles
  • diabetes
  • vascular endothelial cells
  • inflammation
  • mammalian target of rapamycin
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