Predictive Properties of Biomarkers GDF-15, NTproBNP, and hs-TnT for Morbidity and Mortality in Patients With Type 2 Diabetes With Nephropathy

Bidadkosh, Arash; Lambooy, Sebastiaan; Heerspink, Hiddo J L; Pena, Michelle J; Henning, Robert H.; Buikema, Hendrik; Deelman, Leo E.

doi:10.2337/dc16-2175

Cited by 48 publications

(31 citation statements)

References 31 publications

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“…The dynamic change of the plasma level of NT-proBNP is correlated with the clinical prognosis of patients with acute decompensated heart failure when they are discharged (10). Meanwhile, it is the independent risk factor for cardiovascular events (11). This study also found the correlation between the plasm level of mtDNA and NT-proBNP after CPB.…”

Section: Discussionsupporting

confidence: 62%

The hidden link between plasma mitochondrial DNA level and cardiac dysfunction after cardiopulmonary bypass

Fan

Zeng

Chen

et al. 2020

Preprint

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Background: To investigate the hidden link between mitochondrial DNA (mtDNA) and cardiac function after cardiopulmonary bypass (CPB), we compared the relationship of plasma mtDNA level and the prevalence of cardiac dysfunction in patients receiving cardiac surgery with CPB.Methods: From September 1st, 2015 to December 1st, 2016, 962 patients who received cardiac surgery with CPB were prospectively comprised in this study. Routine blood test and examinations for blood biochemistry, NT-proBNP and mtDNA were arranged in half an hour when patients were transferred into intensive care unit (ICU). The clinical outcomes related to the cardiac function were determined by at least two senior doctors responsible for ICU. The data were inputted with double check and the inner logic of these data was set to establish the database. SAS 9.4, R 3.2.4 and SPSS 21.0 were used in data analysis.Results: Of the 962 patients (mean [SD] age, 51.6 [12.5] years; 459 [47.7%] male) comprised in this study, 692 patients received cardiac valve surgery, 83 patients received coronary artery bypass grafting (CABG), 58 patients received CABG and cardiac valve surgery at the same time, 70 patients received surgery on ascending aorta, 35 patients received surgery for simple congenital heart diseases and 15 patients received other types of surgery. The prevalence of cardiac dysfunction in this study is 9.25%. The level of mtRNA among patients with cardiac dysfunction and patients without cardiac dysfunction has no statistical significance (t=-1.42, P=0.1565). There was an obvious positive liner correlation between the level of plasma mtDNA and NT-proBNP in patients receiving CPB (r=0.1291, P=0.0386). There was an obvious positive liner correlation between the level of plasma mtDNA and APACHE II score in patients receiving CPB (r=0.2133, P<0.0001).Conclusions: The level of plasma mtDNA was closely related with the cardiac function and illness severity in patients receiving cardiac surgery with CPB.

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Section: Discussionsupporting

confidence: 62%

The hidden link between plasma mitochondrial DNA level and cardiac dysfunction after cardiopulmonary bypass

Fan

Zeng

Chen

et al. 2020

Preprint

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“…In addition, our top "core sSASP" biomarker candidates have been identified as disease biomarkers in human studies. For example, human cohort studies have reported GDF15 as a biomarker of cardiovascular disease, cardiovascular and cancer mortality and morbidity, renal disease, and all-cause mortality independent of cardiovascular mortality [60][61][62][63][64][65][66], as well as a driver of senescence-associated colon cancer metastasis [67]. Additionally, two of the top core sSASP proteins identified by an unbiased k-means clustering algorithm-STC1 and MMP1 (Fig 7B and 7C)-were reported as significant aging biomarkers [48].…”

Section: Discussionmentioning

confidence: 99%

A proteomic atlas of senescence-associated secretomes for aging biomarker development

et al. 2020

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The senescence-associated secretory phenotype (SASP) has recently emerged as a driver of and promising therapeutic target for multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically assessed by a few dozen secreted proteins, has been greatly underestimated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present the "SASP Atlas," a comprehensive proteomic database of soluble proteins and exosomal cargo SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins but also includes a subset of proteins elevated in all SASPs. Our analyses identify several candidate biomarkers of cellular senescence that overlap with aging markers in human plasma, including Growth/differentiation factor 15 (GDF15), stanniocalcin 1 (STC1), and serine protease inhibitors (SERPINs), which significantly correlated with age in plasma from a human cohort, the Baltimore Longitudinal Study of Aging (BLSA). Our findings will facilitate the identification of proteins characteristic of senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus, and tissue of origin of senescent cells in vivo.

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“…Of these markers, the authors noted that 20 proteins (9.2%) are present in the originally-defined SASP (Coppé et al, 2008 (Figure 6A). In addition to aging, various large cohort studies identified GDF15 as a biomarker of cardiovascular disease, cardiovascular and cancer mortality and morbidity, renal disease, and all-cause mortality independent of cardiovascular mortality (Bidadkosh et al, 2017;Daniels et al, 2011;Ho et al, 2012Ho et al, , 2013Rohatgi et al, 2012;Wallentin et al, 2013;Wollert et al, 2017).…”

Section: The Sasp Contains Potential Aging and Disease Biomarkersmentioning

confidence: 99%

A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development

Basisty

Kale

Jeon

et al. 2019

Preprint

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276

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The senescence-associated secretory phenotype (SASP) has recently emerged as both a driver of, and promising therapeutic target for, multiple age-related conditions, ranging from neurodegeneration to cancer. The complexity of the SASP, typically monitored by a few dozen secreted proteins, has been greatly underappreciated, and a small set of factors cannot explain the diverse phenotypes it produces in vivo. Here, we present 'SASP Atlas', a comprehensive proteomic database of soluble and exosome SASP factors originating from multiple senescence inducers and cell types. Each profile consists of hundreds of largely distinct proteins, but also includes a subset of proteins elevated in all SASPs. Based on our analyses, we propose several candidate biomarkers of cellular senescence, including GDF15, STC1 and SERPINs. This resource will facilitate identification of proteins that drive specific senescence-associated phenotypes and catalog potential senescence biomarkers to assess the burden, originating stimulus and tissue of senescent cells in vivo. Figure 4. Renal epithelial cells and fibroblasts express distinct sSASPs. A) Venn diagram comparing proteins increased in the sSASP of senescent fibroblasts vs senescent epithelial cells induced by X-irradiation. B) Venn diagram comparing protein increases in the fibroblast sSASP vs decreases in the epithelial sSASP. C) Pathway and network analysis of proteins highly secreted by senescent fibroblasts and epithelial cells. C) Pathway and network analysis of proteins significantly increased in the fibroblast sSASP but significantly decreased in the epithelial cell sSASP.

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Predictive Properties of Biomarkers GDF-15, NTproBNP, and hs-TnT for Morbidity and Mortality in Patients With Type 2 Diabetes With Nephropathy

Abstract: Biomarkers GDF-15, NTproBNP, and hs-TnT associate independently with renal risk, whereas NTproBNP independently predicts cardiovascular risk.

Cited by 48 publications

References 31 publications

The hidden link between plasma mitochondrial DNA level and cardiac dysfunction after cardiopulmonary bypass

The hidden link between plasma mitochondrial DNA level and cardiac dysfunction after cardiopulmonary bypass

A proteomic atlas of senescence-associated secretomes for aging biomarker development

A Proteomic Atlas of Senescence-Associated Secretomes for Aging Biomarker Development

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