Wang, G-H;
Ma, K-L;
Zhang, Y;
Hu, Z-B;
Liu, L;
Lu, J;
Chen, P-P;
... Liu, B-C; + view all
(2019)
Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway.
Acta Pharmacologica Sinica
, 40
(4)
pp. 468-476.
10.1038/s41401-018-0186-4.
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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.
| Type: | Article |
|---|---|
| Title: | Platelet microparticles contribute to aortic vascular endothelial injury in diabetes via the mTORC1 pathway |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41401-018-0186-4 |
| Publisher version: | https://doi.org/10.1038/s41401-018-0186-4 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| Keywords: | Science & Technology, Physical Sciences, Life Sciences & Biomedicine, Chemistry, Multidisciplinary, Pharmacology & Pharmacy, Chemistry, platelet microparticles, diabetes, vascular endothelial cells, inflammation, mammalian target of rapamycin, CIRCULATING MICROPARTICLES, INFLAMMATORY RESPONSE, MAMMALIAN TARGET, ATHEROSCLEROSIS, MICROVESICLES, DYSFUNCTION, GLYCOCALYX, TYPE-1, ACTIVATION, MECHANISMS |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10090305 |
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