C1q/TNF-related protein 5 contributes to diabetic vascular endothelium dysfunction through promoting Nox-1 signaling

Liu, Jing; Meng, Zhijun; Gan, Lu; Guo, Rui; Gao, Jiajia; Liu, Caihong; Zhu, Di; Liu, Demin; Zhang, Ling; Zhang, Zhen; Xie, Dina; Jiao, Xiangying; Lopez, Bernard L.; Christopher, Theodore A.; Ma, Xin‐Liang; Cao, Ji-Min; Wang, Yajing

doi:10.1016/j.redox.2020.101476

Cited by 25 publications

(18 citation statements)

References 45 publications

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“…The origin of atherosclerosis is related to lipid metabolism alterations, chronic inflammation, and oxidative stress. Many studies have demonstrated that several CTRPs are involved in regulating the pathophysiological progression of atherosclerosis [ 21 , 22 ]. In particular, current research indicates that various CTRPs are involved in the development and progression of atherosclerosis by regulating inflammation response, lipid metabolism, and vascular smooth muscle cell (VSMC) proliferation [ 23 , 24 , 25 ].…”

Section: Ctrps and Vascular Diseasesmentioning

confidence: 99%

“…gCTRP is one of the signaling molecules (along with HFD and HGHL) that commonly activates expression of Nox1, which is implicated in the pathogenesis of cardiovascular diseases. Research reasoned that gCTRP5 activates the mitochondrial apoptotic signal of EC in diabetes, which is blocked by the silencing Nox1 gene [ 21 ]. This study’s authors suggest that interventions blocking gCTRP5 may protect diabetic EC function, ultimately protecting against diabetic cardiovascular complications [ 21 ].…”

Section: Ctrps and Vascular Diseasesmentioning

confidence: 99%

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C1q Complement/Tumor Necrosis Factor-Associated Proteins in Cardiovascular Disease and COVID-19

et al. 2021

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With continually improving treatment strategies and patient care, the overall mortality of cardiovascular disease (CVD) has been significantly reduced. However, this success is a double-edged sword, as many patients who survive cardiovascular complications will progress towards a chronic disorder over time. A family of adiponectin paralogs designated as C1q complement/tumor necrosis factor (TNF)-associated proteins (CTRPs) has been found to play a role in the development of CVD. CTRPs, which are comprised of 15 members, CTRP1 to CTRP15, are secreted from different organs/tissues and exhibit diverse functions, have attracted increasing attention because of their roles in maintaining inner homeostasis by regulating metabolism, inflammation, and immune surveillance. In particular, studies indicate that CTRPs participate in the progression of CVD, influencing its prognosis. This review aims to improve understanding of the role of CTRPs in the cardiovascular system by analyzing current knowledge. In particular, we examine the association of CTRPs with endothelial cell dysfunction, inflammation, and diabetes, which are the basis for development of CVD. Additionally, the recently emerged novel coronavirus (COVID-19), officially known as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has been found to trigger severe cardiovascular injury in some patients, and evidence indicates that the mortality of COVID-19 is much higher in patients with CVD than without CVD. Understanding the relationship of CTRPs and the SARS-CoV-2-related damage to the cardiovascular system, as well as the potential mechanisms, will achieve a profound insight into a therapeutic strategy to effectively control CVD and reduce the mortality rate.

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Section: Ctrps and Vascular Diseasesmentioning

confidence: 99%

Section: Ctrps and Vascular Diseasesmentioning

confidence: 99%

C1q Complement/Tumor Necrosis Factor-Associated Proteins in Cardiovascular Disease and COVID-19

et al. 2021

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“…The administration of CTRP1, 2, 4, 6, or 7 did not induce any vasorelaxation [15]. Besides, the biologically active domain of CTRP3, CTRP5 and CTRP9 of humans is a C-terminal C1q-like globular domain (gCTRP3, gCTRP5 and gCTRP9) and related experiments were performed as previously described [11,17,18]. Therefore, gCTRP3, gCTRP5 and gCTRP9 were used in our experiments.…”

Section: Ctrp3-induced Microvascular Relaxation Is Endothelium-dependmentioning

confidence: 99%

C1q/TNF–Related Protein-3 attenuates endothelial dysfunction in diabetic retinopathy via the Nitric Oxide signaling pathway

Yan

Cao

Wang

et al. 2020

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Background Diabetic retinopathy (DR) is a severe microvasculature complication of diabetes. Restoration of dysfunctional endothelial cells represents a promising approach to treatment of DR. It has been demonstrated that a number of CTRP (C1q/tumor necrosis factor-related protein) members improves vascular endothelial function of the aortic vasculature. However, the role of CTRPs in the treatment of DR remains largely unresolved. Therefore, the aim of this study was to determine whether members of the CTRP family improve diabetes-induced endothelial dysfunction of retinal vasculature, thus exhibiting a protective effect against diabetic injury of retina. Methods The vasoactivity of currently identified murine CTRP family members was assessed in vascular rings and the underlying molecular mechanisms elucidated in human retinal microvascular endothelial cells. We then mimicked diabetic retinopathy both in vitro and in vivo, after which they were treated with CTRP3, and the vasoactivity, apoptotic cell death and vascular leakage in the retina were evaluated. Discovery-drive approaches followed by cause-effect analysis were used to uncover the molecular mechanisms of CTRP3. Results Our results demonstrate that CTRP3, CTRP5, and CTRP9 exert vasorelaxant effects on macro- and micro-vessels, with CTRP3 being the most potent in micro-vessels. The effects of CTRP3 were found to be endothelium-dependent via the AdipoR1/AMPK/eNOS/Nitric Oxide (NO) pathway. In in vitro microvascular reactivity studies, CTRP3 successfully improved high glucose/high lipid-induced impairment of endothelium-dependent vasodilatation. Blockade of either AMPK or eNOS completely abolished the previously observed effects of CTRP3. In addition, in the murine diabetic retinopathy model, CTRP3 treatment increased endothelium-dependent relaxation and NO levels in microvessels, and inhibited apoptotic cell death and vascular leakage in the retina. Finally,blockade of NO synthesis completely abolished the effects of CTRP3 that had been measured previously. Conclusion Taken together, our findings reveal that the AdipoR1/AMPK/eNOS/NO signaling pathway, through which CTRP3 reverses endothelial dysfunction of the microvasculature by normalization of impaired vasodilatation, represents a novel intervention effective against diabetic injury of retina.

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“…Apoe knockout mice (male Apoe-/-mice, 8-10 weeks old) were utilized in this study. The mice were either fed the normal diet (ND), or high-fat diet (HFD) (60% kcal fat, 20% kcal protein, 20% kcal carbohydrate, Cat #D12492; Research Diets) for 20 weeks to induce atherosclerosis according to the previous study [17]. Total RNA was extracted from Apoe -/mice's artery using Trizol reagent (Invitrogen, Carlsbad, CA).…”

Section: Laboratory Animals and Approved By The Thomas Jefferson Univmentioning

confidence: 99%

Identification of Key Candidate Biomarkers and Pathways in Atherosclerosis

Meng

Gao

Liang

et al. 2020

Preprint

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Background Atherosclerosis is the leading cause of cardiovascular disease worldwide for which lacks effective prevention and therapeutic strategy. Therefore, clinical indicators for early diagnosis and screening are in great need. The present study aimed to elucidate the key genetic signatures and pathways identifying the key candidate biomarker in atherosclerosis by integrative bioinformatics analysis combining with experimental assay. Methods The gene expression profiles (GSE30169, GSE6584) were achieved from the Gene Expression Omnibus database. Functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to examine the biological functions of identified differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was mapped using Cytoscape software. Results 91 DEGs were identified, including 68 up-regulated genes and 23 down-regulated genes. Functional enrichment analysis indicated that DEGs genes were significantly enriched in ferroptosis, TNF signaling pathway, IL-17 signaling pathway. 12 nodes with the highest degrees were selected as hub genes. CCL2, CXCL1, IL6, and DUSP1 can serve as a sensitive diagnostic indicator for the early stage of atherosclerosis; CEBPB and HMOX1 can serve as a diagnostic indicator for diabetic atherosclerosis; TRIB3 is a sensitive marker indicating atherosclerosis risks in diabetic women group.Conclusions In conclusion, we have identified key candidate genes that indicate the diagnosis of patients with atherosclerosis, and these genes may serve as potential therapeutic or drug development targets for atherosclerosis.

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C1q/TNF-related protein 5 contributes to diabetic vascular endothelium dysfunction through promoting Nox-1 signaling

Cited by 25 publications

References 45 publications

C1q Complement/Tumor Necrosis Factor-Associated Proteins in Cardiovascular Disease and COVID-19

C1q Complement/Tumor Necrosis Factor-Associated Proteins in Cardiovascular Disease and COVID-19

C1q/TNF–Related Protein-3 attenuates endothelial dysfunction in diabetic retinopathy via the Nitric Oxide signaling pathway

Identification of Key Candidate Biomarkers and Pathways in Atherosclerosis

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