ADAMTS-7 Expression Increases in the Early Stage of Angiotensin II-Induced Renal Injury in Elderly Mice

Gao, Yanxiang; Yu, Chenghao; Lu, Jianhua; Gao, Hongmei; Geng, Long; Kong, Wei; Zheng, Jingang

doi:10.1159/000355758

Cited by 18 publications

(11 citation statements)

References 24 publications

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“…Indeed, ADAMTS-7 has been shown to promote vascular remodeling via thrombospondin-1 [23]. ADAMTS-7 levels were correlated with inflammatory markers such as TNF-α and NF-κB in different inflammatory conditions and diseases [24][25][26], as well as in organ injury such as angiotensin-II renal injury [27]. Interestingly, recent findings suggested that activation of M1 but not M2 macrophages plays an important role in cardiac remodeling after myocardial infarction in rats [28].…”

Section: Discussionmentioning

confidence: 99%

Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction

Wang²,

Yu³

et al. 2016

Cell Physiol Biochem

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Background/Aims: High ADAMTS-7 levels are associated with acute myocardial infarction (AMI), although its involvement in ventricular remodeling is unclear. In this study, we investigated the association between ADAMTS-7 expression and cardiac function in a rat AMI model. Methods: Sprague-Dawley rats were randomized into AMI (n = 40) and sham (n = 20) groups. The left anterior descending artery was sutured to model AMI. Before surgery and 7, 14, 28, and 42 days post-surgery, ADAMTS-7 and brain natriuretic peptide (BNP), and cartilage oligomeric matrix protein (COMP) were assessed by ELISA, western blot, real-time RT-PCR, and/or immunohistochemistry. Cardiac functional and structural parameters were assessed by M-mode echocardiography. Results: After AMI, plasma ADAMTS-7 levels increased, peaking on day 28 (AMI: 13.2 ± 6.3 vs. sham: 3.4 ± 1.3 ng/ml, P < 0.05). Compared with the sham group, ADAMTS-7 expression was higher in the infarct zone at day 28. COMP present in normal myocardium was degraded by day 28 post-AMI. Plasma ADAMTS-7 correlated positively with BNP (r = 0.642, P = 0.025), left ventricular end-diastolic diameter (r = 0.695, P = 0.041), left ventricular end-systolic diameter (r = 0.710, P = 0.039), left ventricular ejection fraction (r = 0.695, P = 0.036), and left ventricular short-axis fractional shortening (r = 0.721, P = 0.024). Conclusions: ADAMTS-7 levels may reflect the degree of ventricular remodeling after AMI.

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Section: Discussionmentioning

confidence: 99%

Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction

Wang²,

Yu³

et al. 2016

Cell Physiol Biochem

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“…For example, THP-1 monocytes show increased ADAMTS-7 expression after stimulation with interferon-γ or TNF-α 11 and cartilage explants increase ADAMTS-7 expression after TNF-α or interleukin-1β stimulation 26 . Furthermore, angiotensin II-treatment of mice associated with inflammatory kidney damage induces renal ADAMTS-7 expression 27 and ADAMTS-7 is elevated in collagen-induced arthritic mice 6 . It is also possible that some of the CD68 stained cells in the analyzed carotid plaques in our study are in fact SMC-derived cells displaying macrophage markers.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis

Bengtsson¹,

Hultman²,

Dunér³

et al. 2017

Sci Rep

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Several large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated. Carotid plaques (n = 206) from patients with and without cerebrovascular symptoms were analyzed for expression of ADAMTS-7 by immunohistochemistry and correlated to components associated with plaque vulnerability. Plaques from symptomatic patients showed increased levels of ADAMTS-7 compared with lesions from asymptomatic patients. High levels of ADAMTS-7 correlated with high levels of CD68-staining and lipid content, but with low smooth muscle cell and collagen content, which together are characteristics of a vulnerable plaque phenotype. ADAMTS-7 levels above median were associated with increased risk for postoperative cardiovascular events. Our data show that ADAMTS-7 is associated with a vulnerable plaque phenotype in human carotid lesions. These data support previous observations of a potential proatherogenic role of ADAMTS-7.Several large-scale genome-wide association studies (GWAS) have identified SNPs in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease (CAD) 1-3 . ADAMTS-7 is a proteolytic enzyme and its best characterized substrate is the cartilage oligomeric protein (COMP) also known as thromobospondin-5 4 . Previous studies have focused on the role of ADAMTS-7 in cartilage degradation, and recently ADAMTS-7 was shown to enhance both osteoarthritis and collagen-induced arthritis in mice 5,6 . In a rodent model of vascular disease, ADAMTS-7 has been implicated in restenosis 7 , which was recently confirmed in two studies using ADAMTS-7-deficient mice 8,9 . The role of ADAMTS-7 in neointima formation is mediated via increased smooth muscle cell (SMC) migration by degradation of COMP and via impaired re-endothelialization 7, 9 . In agreement with this, the SNP (identified by GWAS) rs3825807 (A to G), leading to a Ser-to-Pro substitution in the prodomain of ADAMTS-7, reduces cleavage of the prodomain of ADAMTS-7, SMC-mediated COMP degradation, and SMC migration 10 . In addition to its role in restenosis, a recent study showed that ADAMTS-7-deficiency significantly reduces atherosclerotic lesion formation in both ApoE −/− and LDLr −/− mice 8 . In cultured SMCs, ADAMTS-7 expression is up-regulated by inflammatory cytokines such as TNF-α, interleukin-1β, reactive oxygen species (H 2 O 2 ), and platelet-derived growth factor-BB, whereas the anti-inflammatory cytokine transforming growth factor-β reduces ADAMTS-7 expression 7,9 . ADAMTS-7 is also expressed in monocytes/macrophages, and int...

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“…Although ADAMTS‐7 related to kidney damage and atherosclerosis, it is suggested that ADAMTS‐1 and ‐14 are associated with fibrosis . Also, it is claimed renal ADAMTS‐7 expression was induced by Ang II in elderly mice and suggested the overexpression of ADAMTS‐7 might contribute to early inflammatory kidney damage associated with aging . In the study of murine remnant kidney model, Yang et al observed a significant increase in the average gene expression of ADAMTS‐1 and several profibrotic genes including MMP‐2, MMP‐9, TIMP‐1 and fibroblast specific protein‐1.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia causes important changes of extracellular matrix biomarkers and ADAMTS proteinases in the adriamycin‐induced renal fibrosis model

et al. 2019

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This study aimed to investigate the role of ADAMTS proteinases and other related ECM markers in the pathogenesis of renal fibrosis, and to investigate the effects of hypoxia upon these biomarkers. The findings of this study demonstrated that hypoxia promotes development of renal fibrosis. ADAMTS proteases may provide some important signals in contributing to the early diagnosis and treatment options for renal fibrosis. ABSTRACT:Aim: Renal fibrosis is a common cause of renal dysfunction with chronic kidney diseases. This process is characterized by excessive production of extracellular matrix (ECM) or inhibition of ECM degradation. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) proteinases, which are widely presented in mammals, have very critical roles in ECM remodelling. We aimed to study the role of ADAMTS proteinases and some of the ECM markers in the pathogenesis of renal fibrosis and to investigate the effects of hypoxia on these biomarkers.Methods: In addition to the control group, Adriamycin (ADR) treated rats were divided into four groups as ADR, sham and two hypoxia groups. Renal nephropathy was assessed biochemical assays, pathological and immunohistochemical staining methods. The expression of ADAMTSs and mRNA were determined using Western blotting and real-time PCR, respectively.

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ADAMTS-7 Expression Increases in the Early Stage of Angiotensin II-Induced Renal Injury in Elderly Mice

Cited by 18 publications

References 24 publications

Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction

Association of ADAMTS-7 Levels with Cardiac Function in a Rat Model of Acute Myocardial Infarction

ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis

Hypoxia causes important changes of extracellular matrix biomarkers and ADAMTS proteinases in the adriamycin‐induced renal fibrosis model

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