PMID- 28900239 OWN - NLM STAT- MEDLINE DCOM- 20190621 LR - 20220331 IS - 2045-2322 (Electronic) IS - 2045-2322 (Linking) VI - 7 IP - 1 DP - 2017 Sep 12 TI - Siglec-5 is a novel marker of critical limb ischemia in patients with diabetes. PG - 11272 LID - 10.1038/s41598-017-11820-x [doi] LID - 11272 AB - Critical Limb Ischemia (CLI) is common but uncommonly diagnosed. Improved recognition and early diagnostic markers for CLI are needed. Therefore, the aim of our study was to identify plasma biomarkers of CLI in patients with type 2 diabetes mellitus (T2DM). In this study, antibody-coated glass slide arrays were used to determine the plasma levels of 274 human cytokines in four matched cases of diabetes with and without CLI. Potential biomarkers were confirmed in an independent cohort by ELISA. After adjusting for confounding risk factors, only plasma level of Siglec-5 remained significantly associated with an increased odds ratio (OR) for diabetes with CLI by binary logistic regression analysis. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off points for Siglec-5 was 153.1 ng/ml. After entering Siglec-5, the AUC was 0.99, which was higher than that of confounding risk factors only (AUC = 0.97, P < 0.05). Siglec-5 was expressed in plaques, but not in healthy artery wall in T2DM patients. Elevated plasma Siglec-5 was independently associated with CLI in T2DM. Plasma Siglec-5 levels are implicated as an early diagnostic marker of CLI in T2DM patients and it may become a target for the prevention or treatment of CLI in diabetes. FAU - Li, Ju-Yi AU - Li JY AD - Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. AD - Department of Pharmacy, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Yang, Xiao-Yan AU - Yang XY AD - Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Wang, Xiu-Fang AU - Wang XF AD - Department of Pain, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Jia, Xiong AU - Jia X AD - Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Wang, Zhong-Jing AU - Wang ZJ AD - Department of Endocrinology, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Deng, Ai-Ping AU - Deng AP AD - Department of Pharmacy, The central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Bai, Xiang-Li AU - Bai XL AD - Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Zhu, Lin AU - Zhu L AD - Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Li, Bing-Hui AU - Li BH AD - Department of Wound Repair, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Feng, Zi-Bo AU - Feng ZB AD - Department of Wound Repair, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Li, Ye AU - Li Y AD - Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Wang, Ling AU - Wang L AD - Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. FAU - Jin, Si AU - Jin S AD - Department of Pharmacology, Hubei Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Jinsi@hust.edu.cn. AD - Department of Endocrinology, Institute of Geriatric Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Jinsi@hust.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170912 PL - England TA - Sci Rep JT - Scientific reports JID - 101563288 RN - 0 (Antigens, CD) RN - 0 (Antigens, Differentiation, Myelomonocytic) RN - 0 (Biomarkers) RN - 0 (Cytokines) RN - 0 (Lectins) RN - 0 (SIGLEC5 protein, human) SB - IM MH - Aged MH - Antigens, CD/*blood MH - Antigens, Differentiation, Myelomonocytic/*blood MH - *Biomarkers MH - Cytokines/blood MH - Diabetes Mellitus, Type 2/*complications MH - Female MH - High-Throughput Screening Assays MH - Humans MH - Ischemia/*blood/diagnosis/*etiology MH - Lectins/*blood MH - Male MH - Middle Aged MH - Odds Ratio MH - Plaque, Atherosclerotic/metabolism MH - Protein Array Analysis MH - ROC Curve MH - Reproducibility of Results MH - Risk Factors PMC - PMC5595823 COIS- The authors declare that they have no competing interests. EDAT- 2017/09/14 06:00 MHDA- 2019/06/22 06:00 PMCR- 2017/09/12 CRDT- 2017/09/14 06:00 PHST- 2017/05/24 00:00 [received] PHST- 2017/08/30 00:00 [accepted] PHST- 2017/09/14 06:00 [entrez] PHST- 2017/09/14 06:00 [pubmed] PHST- 2019/06/22 06:00 [medline] PHST- 2017/09/12 00:00 [pmc-release] AID - 10.1038/s41598-017-11820-x [pii] AID - 11820 [pii] AID - 10.1038/s41598-017-11820-x [doi] PST - epublish SO - Sci Rep. 2017 Sep 12;7(1):11272. doi: 10.1038/s41598-017-11820-x.