Increased serum C1q/TNF-related protein 4 concentration in patients with acute coronary syndrome

Dai, Yunlang; Zhou, Jing; Niu, Lijuan; Hu, Junting; Han, Junxia

doi:10.1016/j.cca.2021.11.015

Cited by 4 publications

(6 citation statements)

References 25 publications

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“…found that CTRP4 reduces food intake by inducing the signal transducer and activator of transcription 3 and nuclear factor‐κB pathways. A recent study reported by Dai et al 64 . showed that CTRP4 amounts are lower in non‐ACS cases compared with ACS patients.…”

Section: Discussionmentioning

confidence: 91%

“…Interestingly, Li et al 25 found that CTRP4 reduces food intake by inducing the signal transducer and activator of transcription 3 and nuclear factor-jB pathways. A recent study reported by Dai et al 64 showed that CTRP4 amounts are lower in non-ACS cases compared with ACS patients. However, Liu et al 65 found that serum CTRP4 levels were decreased in newly diagnosed type 2 diabetes mellitus patients compared with healthy controls.…”

Section: Discussionmentioning

confidence: 91%

“…A recent study reported by Dai et al . 64 showed that CTRP4 amounts are lower in non‐ACS cases compared with ACS patients. However, Liu et al .…”

Section: Discussionmentioning

confidence: 96%

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C1q tumor necrosis factor‐related protein 4 is associated with coronary artery disease in patients with type 2 diabetes

Gao

Qiu

Sun

et al. 2022

J of Diabetes Invest

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Aims/Introduction: To evaluate the correlation of circulating C1q tumor necrosis factor-related protein 4 (CTRP4) with coronary artery disease (CAD) in type 2 diabetes mellitus patients. Methods: A total of 240 individuals with type 2 diabetes mellitus were enrolled in our center between January 2020 and December 2020. They were assigned into two groups, including the CAD and non-CAD groups, based on coronary angiography or computed tomography angiography findings. Serum CTRP4 levels were detected by an enzymelinked immunosorbent assay kit. The association of CTRP4 with CAD was determined by logistic regression analysis. The predictive value of CTRP4 for CAD was calculated by receiver operating characteristic curve analysis. Results: Median serum CTRP4 amounts were markedly elevated in the CAD group in comparison with the non-CAD group (10.37 vs 3.75 ng/mL, P < 0.01). Binary logistic regression showed that CTRP4 was associated with CAD and even the amount of coronary artery lesions (P < 0.05). In receiver operating characteristic curve analysis, the area under the receiver operating characteristic curve was greater for CTRP4 compared with HbA1c or CRP (0.87 vs 0.74, 0.87 vs 0.80, P < 0.01). The area under the curve for CTRP4 and glycated hemoglobin in combination was larger than that obtained for CTRP4 combined with CRP (0.91 vs 0.87, P < 0.01). According to the maximum Youden index criteria, the optimal cut-off of CTRP4 was 5.42 ng/mL, which yielded a sensitivity of 84.4% and a specificity of 76.7% in predicting CAD in type 2 diabetes mellitus patients. Conclusions: Serum CTRP4 levels are positively correlated with CAD occurrence and severity. Combining CTRP4 and glycated hemoglobin has a better predictive value for CAD in type 2 diabetes mellitus patients.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 91%

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C1q tumor necrosis factor‐related protein 4 is associated with coronary artery disease in patients with type 2 diabetes

Gao

Qiu

Sun

et al. 2022

J of Diabetes Invest

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“…The study suggested that C1QTNF4 interacts with nucleolin via its second C1q‐like domain and nucleolin's C terminus in these cells. Additionally, a recent study has shown that serum C1QTNF4 level may be a potential biomarker for acute coronary syndrome 19 . However, the role of C1QTNF4 in vascular physiology and disease processes remains unclear.…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, a recent study has shown that serum C1QTNF4 level may be a potential biomarker for acute coronary syndrome. 19 However, the role of C1QTNF4 in vascular physiology and disease processes remains unclear.…”

Section: Introductionmentioning

confidence: 99%

C1q/TNF‐related protein 4 mediates proliferation and migration of vascular smooth muscle cells during vascular remodelling

Liu

Long

et al. 2023

Clinical & Translational Med

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Background Vascular remodelling is an essential pathophysiological state in many circulatory diseases. Abnormal vascular smooth muscle cell (VSMC) behaviour leads to neointimal formation and may eventually results in major adverse cardiovascular events. The C1q/TNF‐related protein (C1QTNF) family is closely associated with cardiovascular disease. Notably, C1QTNF4 has unique two C1q domains. However, the role of C1QTNF4 in vascular diseases remains unclear. Methods C1QTNF4 expression was detected in human serum and artery tissues using ELISA and multiplex immunofluorescence (mIF) staining. Scratch assay, transwell assay and confocal microscopy were used to investigate C1QTNF4 effects on VSMC migration. EdU incorporation, MTT assay and cell counting experiment revealed C1QTNF4 effects on VSMC proliferation. C1QTNF4‐transgenic, C1QTNF4−/− and AAV9‐mediated VSMC‐specific C1QTNF4 restoration C1QTNF4−/‐ mouse and rat disease models were generated. RNA‐seq, quantitative real‐time PCR, western blot, mIF, proliferation and migration assays were used to investigate the phenotypic characteristics and underlying mechanisms. Results Serum C1QTNF4 levels were decreased in patients with arterial stenosis. C1QTNF4 shows colocalisation with VSMC in human renal arteries. In vitro, C1QTNF4 inhibits VSMC proliferation and migration and alters VSMC phenotype. In vivo, an adenovirus‐infected rat balloon injury model, C1QTNF4‐transgenic and C1QTNF4−/− mouse wire‐injury models with or without VSMC‐specific C1QTNF4 restoration were established to mimic the VSMC repair and remodelling. The results show that C1QTNF4 decreases intimal hyperplasia. Especially, we displayed the rescue effect of C1QTNF4 in vascular remodelling using AAV vectors. Next, transcriptome analysis of artery tissue identified the potential mechanism. In vitro and in vivo experiments confirm that C1QTNF4 ameliorates neointimal formation and maintains vascular morphology by downregulating the FAK/PI3K/AKT pathway. Conclusions Our study demonstrated that C1QTNF4 is a novel inhibitor of VSMC proliferation and migration that acts by downregulating the FAK/PI3K/AKT pathway, thus protecting blood vessels from abnormal neointima formation. These results provide new insights into promising potent treatments for vascular stenosis diseases.

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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

Gao,

Rouzi,

Zhang

et al. 2024

Acta Diabetol

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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-α and promote the release of NO in HUVEC supernatants, with suppression of NF-κB 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-κB and STAT3 signaling pathways.

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Increased serum C1q/TNF-related protein 4 concentration in patients with acute coronary syndrome

Cited by 4 publications

References 25 publications

C1q tumor necrosis factor‐related protein 4 is associated with coronary artery disease in patients with type 2 diabetes

C1q tumor necrosis factor‐related protein 4 is associated with coronary artery disease in patients with type 2 diabetes

C1q/TNF‐related protein 4 mediates proliferation and migration of vascular smooth muscle cells during vascular remodelling

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

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