Exp Clin Endocrinol Diabetes 2021; 129(08): 560-565
DOI: 10.1055/a-0981-6023
Article

Activation of Factor XII and Kallikrein-Kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy

Da Young Song
1   Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Ja-Yoon Gu
1   Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Hyun Ju Yoo
1   Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
,
Young Il Kim
2   Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
,
Il Sung Nam-Goong
2   Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
,
Eun Sook Kim
2   Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea
,
Hyun Kyung Kim
1   Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea
› Author Affiliations

Abstract

Background In diabetic retinopathy (DR), neutrophil extracellular traps (NET) and kallikrein-kinin system are considered as contributing factors. However, the detail activation mechanisms has not been fully understood. Since the NET could provide negative-charged surface for factor XII activation and the activated factor XII (XIIa) can initiate kallikrein-kinin system, this study investigated whether patients with DR show activation of NET, factor XII and kallikrein-kinin system.

Methods The markers related to NET (DNA-histone complex) and kallikrein-kinin system (high-molecular-weight kininogen, prekallikrein, bradykinin) and factor XIIa were measured in 253 patients with diabetes. To access ex vivo effect of glucose, DNA-histone complex and factor XIIa were measured in whole blood stimulated by glucose.

Results The circulating level of DNA-histone complex and factor XIIa were significantly higher in patients with DR than those without DR. In logistic regression analysis, DNA-histone complex, factor XIIa, and high-molecular-weight kininogen were the risk factors of DR. In recursive partitioning analysis, among patients with diabetes duration less than 10 years, patients with high level of DNA-histone complex (>426 AU) showed high risk of DR. In ex vivo experiment, glucose significantly elevated both DNA-histone complex and factor XIIa.

Conclusion Our findings suggest that activation of factor XII and kallikrein-kinin system combined with NET formation actively occur in patients with DR and circulating levels of DNA-histone complex, factor XIIa and HMWK can be potential biomarkers to estimate the risk of DR. Strategies against factor XII activation may be beneficial to inhibit DR.



Publication History

Received: 25 June 2019
Received: 19 July 2019

Accepted: 22 July 2019

Article published online:
19 August 2019

© 2019. Thieme. All rights reserved.

© Georg Thieme Verlag KG
Stuttgart · New York

 
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