PMID- 38286878 OWN - NLM STAT- MEDLINE DCOM- 20240427 LR - 20240430 IS - 1432-5233 (Electronic) IS - 0940-5429 (Print) IS - 0940-5429 (Linking) VI - 61 IP - 5 DP - 2024 May TI - Association of serum CTRP4 levels with vascular endothelial function in patients with type 2 diabetes mellitus: CTRP4 ameliorating inflammation, proliferation and migration in human umbilical vein endothelial cells. PG - 565-575 LID - 10.1007/s00592-023-02228-3 [doi] AB - OBJECTIVE: We investigated the correlation between serum C1q/TNF-related protein 4 (CTRP4) level and flow-mediated dilation (FMD) in patients with type 2 diabetes mellitus (T2DM), and evaluated the biological effects of CTRP4 on human umbilical vein endothelial cells (HUVECs). METHODS: A group of 165 patients diagnosed with T2DM were included in this study. Endothelial function was measured with the examination of brachial artery FMD. ELISA kit was used to measure the levels of CTRP4 in serum. HUVECs were stimulated with recombinant CTRP4 protein to assess its biological functions. RESULTS: The levels of CTRP4 showed a significant variation among three groups based on FMD tertiles (p = 0.001). What's more, FMD had a significant difference among three CTRP4 tertile groups (p < 0.05) and was negatively related to serum CTRP4 levels (r = -0.270, p < 0.001). In T2DM patients, logistic regression analysis demonstrated that CTRP4 was the primary influence factor of low FMD (p < 0.01). In receiver operating characteristic curve analysis, the area under the curve of CTRP4 for predicting low FMD was 0.66 (95%CI 0.58-0.75). When stimulated HUVECs with recombinant CTRP4 protein, we found that CTRP4 could concentration-dependently ameliorate proliferation and migration of HUVECs in wounding healing and transwell assay. This protein could also decrease the expression of IL-6 and TNF-alpha and promote the release of NO in HUVEC supernatants, with suppression of NF-kappaB and STAT3 phosphorylation. CONCLUSIONS: Serum CTRP4 concentrations were negatively associated with FMD. CTRP4 alleviated proliferation, migration and inflammation in HUVECs through the suppression of NF-kappaB and STAT3 signaling pathways. CI - (c) 2024. The Author(s). FAU - Gao, Jie AU - Gao J AUID- ORCID: 0000-0003-3330-2219 AD - Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 LanXi Road, Shanghai, 200062, China. FAU - Rouzi, Mai Re YanMu AU - Rouzi MRY AD - School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Zhang, Huihui AU - Zhang H AD - School of Medical and Life Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China. FAU - Cai, Xinghua AU - Cai X AD - Shanghai Putuo Center School of Clinical Medicine, Anhui Medical University, Hefei, Anhui, China. FAU - Xu, Bilin AU - Xu B AD - Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 LanXi Road, Shanghai, 200062, China. FAU - Lu, Jun AU - Lu J AD - Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 LanXi Road, Shanghai, 200062, China. FAU - Lei, Tao AU - Lei T AD - Department of Endocrinology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, 164 LanXi Road, Shanghai, 200062, China. taolei_12@sina.com. LA - eng GR - 2020tszk01/Clinical Characteristic of Health System in Putuo District, Shanghai/ GR - ZK2019B16/Shanghai Medical Key Specialties/ GR - ptkwws202003/Science, Technology Innovation Project of Putuo District Health System/ GR - ptkwws201911/Science, Technology Innovation Project of Putuo District Health System/ GR - 20204Y0154/Research Project of Shanghai Municipal Health Care Commission/ GR - 22-LY-03/Scientific Research of Shanghai Sixth Hospital Consortium/ PT - Journal Article DEP - 20240129 PL - Germany TA - Acta Diabetol JT - Acta diabetologica JID - 9200299 RN - 0 (Adipokines) RN - 0 (NF-kappa B) SB - IM MH - Humans MH - *Human Umbilical Vein Endothelial Cells MH - *Diabetes Mellitus, Type 2/blood MH - Male MH - Female MH - Middle Aged MH - *Cell Movement MH - *Cell Proliferation MH - *Inflammation MH - Endothelium, Vascular/metabolism MH - Aged MH - Adipokines/blood MH - Adult MH - NF-kappa B/metabolism PMC - PMC11055794 OTO - NOTNLM OT - CTRP4 OT - Endothelial function OT - Flow-mediated dilation OT - Type 2 diabetes mellitus COIS- The authors declare that there are no conflict of interests. EDAT- 2024/01/30 00:42 MHDA- 2024/04/28 07:24 PMCR- 2024/01/29 CRDT- 2024/01/29 23:18 PHST- 2023/10/31 00:00 [received] PHST- 2023/12/18 00:00 [accepted] PHST- 2024/04/28 07:24 [medline] PHST- 2024/01/30 00:42 [pubmed] PHST- 2024/01/29 23:18 [entrez] PHST- 2024/01/29 00:00 [pmc-release] AID - 10.1007/s00592-023-02228-3 [pii] AID - 2228 [pii] AID - 10.1007/s00592-023-02228-3 [doi] PST - ppublish SO - Acta Diabetol. 2024 May;61(5):565-575. doi: 10.1007/s00592-023-02228-3. Epub 2024 Jan 29.