Article

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

Authors: Gui-hua Wang1, Kun-ling Ma1, Yang Zhang1, Ze-bo Hu1, Liang Liu1, Jian Lu1, Pei-pei Chen1, Chen-chen Lu1, Xiong-zhong Ruan2, Bi-cheng Liu1
1 Institute of Nephrology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China
2 Center for Nephrology, University College London (UCL) Medical School, Royal Free Campus, London NW3 2PF, UK
Correspondence to: Gui-hua Wang: klma05@163.com,
DOI: 10.1038/s41401-018-0186-4
Received: 6 August 2018
Accepted: 10 October 2018
Advance online: 16 November 2018

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.
Keywords: platelet microparticles; diabetes; vascular endothelial cells; inflammation; mammalian target of rapamycin

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