Putative targeting of matrix metalloproteinase-8 in atherosclerosis

Ye, Shu

doi:10.1016/j.pharmthera.2014.11.007

Cited by 25 publications

(28 citation statements)

References 143 publications

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“…Gene targeting studies also demonstrated reduced atherosclerosis development in MMP8 knockout mice. 49 A multicenter cohort study demonstrated increased serum MMP-8 levels in septic patients admitted to the ICU. 50 …”

Section: Discussionmentioning

confidence: 99%

Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients

Sun

Daniels

et al. 2018

Kidney International Reports

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IntroductionCurrently, no effective therapies exist to reduce the high mortality associated with dialysis-dependent acute kidney injury (AKI-D). Serum biomarkers may be useful in understanding the pathophysiological processes involved with AKI and the severity of injury, and point to novel therapeutic targets.MethodsStudy day 1 serum samples from 100 patients and day 8 samples from 107 patients enrolled in the Veteran’s Affairs/National Institutes of Health Acute Renal Failure Trial Network study were analyzed by the slow off-rate modified aptamers scan proteomic platform to profile 1305 proteins in each sample. Patients in each cohort were classified into tertiles based on baseline biomarker measurements. Cox regression analyses were performed to examine the relationships between serum levels of each biomarker and mortality.ResultsChanges in the serum levels of 54 proteins, 33 of which increased and 21 of which decreased, were detected when comparing samples of patients who died in the first 8 days versus patients who survived >8 days. Among the 33 proteins that increased, higher serum levels of fibroblast growth factor-23 (FGF23), tissue plasminogen activator (tPA), neutrophil collagenase (matrix metalloproteinase-8), and soluble urokinase plasminogen activator receptor, when stratified by tertiles, were associated with higher mortality. The association with mortality persisted for each of these proteins after adjusting for other potential risk factors, including age, sex, cardiovascular sequential organ failure assessment score, congestive heart failure, and presence of diabetes. Upper tertile levels of FGF23, tPA, and interleukin-6 on day 8 were associated with increased mortality; however, FGF23 barely lost significance after multivariable adjustment.ConclusionsOur results underscore an emerging proteomics tool capable of identifying low-abundance serum proteins important not only in the pathogenesis of AKI-D, but which is also helpful in discriminating AKI-D patients with high mortality.

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Section: Discussionmentioning

confidence: 99%

Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients

Sun

Daniels

et al. 2018

Kidney International Reports

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“…Activated MMP-8 can decrease collagen matrix and damage its structure, giving rise to the expression of fibrosis and high expression of collagen I and III. 14 , 15 MMP-14 is a transmembrane protein, and MMP-11 can be soluble in cellular microenvironment. MMP-11 is a substrate of MMP-14, and it is able to prevent MMP-11 enzymatic activity.…”

Section: Discussionmentioning

confidence: 99%

H₂S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression

Zeng

et al. 2016

Renal Failure

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Nephropathy develops in many patients with type 1 diabetes mellitus (T1DM). However, the specific mechanisms and therapies remain unclear. For this purpose we investigated the effects of hydrogen sulfide (H2S) on renal fibrosis in streptozotocin (STZ) induced diabetic rats and its underlying mechanisms.Experimental rats were randomly divided into four groups: Control group (normal rats), DM group (diabetes rats), DM + NaHS group [diabetes rats treated with sodium hydrosulfide (NaHS)], and NaHS group (normal rats treated with NaHS). The diabetic models were established by intraperitoneal injection of STZ. The NaHS-treated rats were injected with NaHS as an exogenous donor of H2S. At the same time, control group and DM group were administrated with equal doses of normal saline (NS). After eight weeks, the rats’ urine samples were collected to measure the renal hydroxyproline content by basic hydrolysis method with a hydroxyproline detection kit. Collagen I and III content was detected by immunohistochemical method, and the pathology morphology of kidney was analyzed by Masson staining. Protein expressions of transforming growth factor beta 1 (TGF-β1), ERK1/2, TIMP1, TIMP2, MMP-2, MMP-7, MMP-8, MMP-11, and MMP-14 were assessed by western blotting. The results showed that significant fibrosis occurred in the kidney of diabetes rats. NaHS treatment downregulated TGF-β1, ERK1/2, TIMP1, TIMP2, MMP-2, MMP-7, MMP-8, MMP-11, and MMP-14 expressions in the kidney of these diabetes rats (p<.01). This result suggests that NaHS treatment could attenuate renal fibrosis by TGF-β1 signaling, and its mechanisms may be correlated with ERK1/2 expression and modulation of MMPs/TIMPs expression. Therefore, H2S may provide a promising option for defensing against diabetic renal fibrosis through TGF-β1 signaling, equilibrating the balance between profibrotic and antifibrotic mediators.

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“…In future, it is likely that more selective treatments will be developed. These should be aimed at inhibiting excess production of specific MMPs, especially the collagenases MMP‐1 (Libby, ) and MMP‐8 (Ye, ) and MMP‐12 (Traylor et al . ), whilst preserving the activity of those MMPs, including MMP‐9, that are primarily involved in vascular repair (Newby, ).…”

Section: Introductionmentioning

confidence: 99%

Metalloproteinase production from macrophages – a perfect storm leading to atherosclerotic plaque rupture and myocardial infarction

Newby

2016

Experimental Physiology

121

108

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Putative targeting of matrix metalloproteinase-8 in atherosclerosis

Cited by 25 publications

References 143 publications

Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients

Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients

H₂S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression

Metalloproteinase production from macrophages – a perfect storm leading to atherosclerotic plaque rupture and myocardial infarction

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Putative targeting of matrix metalloproteinase-8 in atherosclerosis

Cited by 25 publications

References 143 publications

Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients

Aptamer-Based Proteomics Identifies Mortality-Associated Serum Biomarkers in Dialysis-Dependent AKI Patients

H2S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression

Metalloproteinase production from macrophages – a perfect storm leading to atherosclerotic plaque rupture and myocardial infarction

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H₂S improves renal fibrosis in STZ-induced diabetic rats by ameliorating TGF-β1 expression