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

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.

Authors+Show Affiliations

Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.Department of Internal Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea.Department of Laboratory Medicine and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31426112

Citation

Song, Da Young, et al. "Activation of Factor XII and Kallikrein-kinin System Combined With Neutrophil Extracellular Trap Formation in Diabetic Retinopathy." Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, 2019.
Song DY, Gu JY, Yoo HJ, et al. Activation of Factor XII and Kallikrein-kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy. Exp Clin Endocrinol Diabetes. 2019.
Song, D. Y., Gu, J. Y., Yoo, H. J., Kim, Y. I., Nam-Goong, I. S., Kim, E. S., & Kim, H. K. (2019). Activation of Factor XII and Kallikrein-kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy. Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association, doi:10.1055/a-0981-6023.
Song DY, et al. Activation of Factor XII and Kallikrein-kinin System Combined With Neutrophil Extracellular Trap Formation in Diabetic Retinopathy. Exp Clin Endocrinol Diabetes. 2019 Aug 19; PubMed PMID: 31426112.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of Factor XII and Kallikrein-kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy. AU - Song,Da Young, AU - Gu,Ja-Yoon, AU - Yoo,Hyun Ju, AU - Kim,Young Il, AU - Nam-Goong,Il Sung, AU - Kim,Eun Sook, AU - Kim,Hyun Kyung, Y1 - 2019/08/19/ PY - 2019/8/20/entrez PY - 2019/8/20/pubmed PY - 2019/8/20/medline JF - Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association JO - Exp. Clin. Endocrinol. Diabetes N2 - 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. SN - 1439-3646 UR - https://www.unboundmedicine.com/medline/citation/31426112/Activation_of_Factor_XII_and_Kallikrein-kinin_System_Combined_with_Neutrophil_Extracellular_Trap_Formation_in_Diabetic_Retinopathy L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/a-0981-6023 DB - PRIME DP - Unbound Medicine ER -