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

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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 (>426AU) 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.
Author(s)
송다영구자윤유현주김영일남궁일성김은숙김현경
Issued Date
2021
Type
Article
Keyword
AgedBiomarkers - bloodDiabetic Retinopathy - bloodDiabetic Retinopathy - diagnosisExtracellular TrapsFactor XII - metabolismFemaleHumansKallikrein-Kinin SystemMaleMiddle Aged
DOI
10.1055/a-0981-6023
URI
https://oak.ulsan.ac.kr/handle/2021.oak/8072
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_crossref_primary_10_1055_a_0981_6023&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Activation%20of%20Factor%20XII%20and%20Kallikrein-Kinin%20System%20Combined%20with%20Neutrophil%20Extracellular%20Trap%20Formation%20in%20Diabetic%20Retinopathy&offset=0&pcAvailability=true
Publisher
EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY DIABETES
Location
독일
Language
영어
ISSN
0947-7349
Citation Volume
129
Citation Number
8
Citation Start Page
560
Citation End Page
565
Appears in Collections:
Medicine > Medicine
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