1. Activation of Factor XII and Kallikrein-Kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy.
- Author
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Song, Da Young, Gu, Ja-Yoon, Yoo, Hyun Ju, Kim, Young Il, Nam-Goong, Il Sung, Kim, Eun Sook, and Kim, Hyun Kyung
- Subjects
DIABETIC retinopathy ,RECURSIVE partitioning ,LOGISTIC regression analysis ,BLOOD sugar ,PEOPLE with diabetes - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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