GDF-15

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NF κB regulates GDF 15 to suppress macrophage surveillance during early tumor development

NF κB regulates GDF 15 to suppress macrophage surveillance during early tumor development

pancreatic cancer development. Supporting this notion, RNA-seq analysis of tumor tissue from 183 PDAC cases from The Cancer Genome Atlas (TCGA) (http://genome-cancer.ucsc.edu) showed that patients with PDAC have higher GDF-15 expression (Supple- mental Figure 2B). In addition, we also evaluated survival data for patients suffering from PDAC obtained from TCGA and found a trend indicating that PDAC patients with elevated GDF-15 expres- sion have a poorer prognosis. This conclusion was also supported by a second data set (13) that revealed that PDAC patients with elevat- ed GDF-15 have a worse outcome compared with those with lower expression of GDF-15 (Figure 2A). However, as is common in clinical studies, several patients from both data sets were censored, mak- ing it hard to evaluate statistical significance of the observed trends. Hence, we combined the 2 data sets, thereby increasing the power of the data, and found that PDAC patients with elevated GDF-15 expression have significantly shorter survival times (Supplemen- tal Figure 2C). Together, these data indicate a clinically relevant trend warranting preclinical studies to investigate the relevance of GDF-15 in pancreatic cancer development. To test this, we gener- ated murine Panc02 pancreatic cancer cell lines stably expressing a GDF-15 shRNA (clones 12 and 15), which significantly silenced Gdf- 15 expression (Supplemental Figure 2D). These clones were cocul- tured with primary, peritoneal macrophages to determine whether GDF-15 was capable of neutralizing the antitumor activity of macro- phages as we had observed with p65 +/+ Ras MEFs. Similarly to what
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Original Article GDF-15 promotes proliferation of vascular smooth muscle cells through MAPK-activated protein kinase pathways

Original Article GDF-15 promotes proliferation of vascular smooth muscle cells through MAPK-activated protein kinase pathways

Abstract: Growth differentiation factor 15 (GDF-15) is a multifunctional member of the TGF-b superfamily. Accumulating evidence indicates that GDF15 is an independent biomarker for the cardiovascular disease, and is closely involved in the development of atherosclerotic lesions induced by ox-LDL, such as inhibition of macrophage infiltration and increase of endothelial cell proliferation, while whether GDF-15 also participates into the VSMCs proliferation is still lack of systemic analysis. In the present study, ox-LDL was found to induce GDF15 expression and secretion in cultured rat VSMCs in a p38- and ERK1/2-dependent manner. Inhibition of ox-LDL-induced GDF-15 expression by siRNA transfection by lentivirus demonstrated that adaptively induced GDF15 played a proliferative role in VSMCs, and overexpression of GDF-15 alone was adequate to induce VSMCs proliferation. Further applica- tion of inhibitors of p38- and ERK1/2 attenuated the GDF-15 expression induced by ox-LDL. All data suggest that GDF15 is a proliferative molecule that gives rise to VSMCs proliferation secondary to ox-LDL stimulation in vitro.
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EFFECT OF THE TRIAZOLE ANALOG TAN ON GDF-15 EXPRESSION IN HUMAN COLORECTAL CANCER HCT116 CELL LINE

EFFECT OF THE TRIAZOLE ANALOG TAN ON GDF-15 EXPRESSION IN HUMAN COLORECTAL CANCER HCT116 CELL LINE

GDF -15 is belonged to the β super family of the transforming growth factor & it is correlated with P53 pathway activation in human CA. GDF_ 15 is engaged in controlling apoptosis & inflammatory response during disease & tissue injury . Normally, GDF-15 expressed in significant amounts by the placenta only ; although it is found in little amounts in some tissues like pancreatic, renal & colonic tissues Materials and methods

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GDF-15 plasma levels in chronic obstructive pulmonary disease are associated with subclinical coronary artery disease

GDF-15 plasma levels in chronic obstructive pulmonary disease are associated with subclinical coronary artery disease

Demographics, smoking history, lung function and cardio- vascular risk were analyzed by GDF-15 tertiles, using t -test or chi-square. We tested association between GDF-15 ter- tiles and CAC burden categories by two strategies. First, we used regression models with CAC as outcome. Second, we developed sequential multinomial logistic regression models including variables grouped in bloc, starting with GDF tertiles, then adjusting for baseline HEART score, then further adjusting for co-morbidities, measures of lung function, and severity of airway disease and emphy- sema. We selected logistic modeling as our main approach because it presents outcome and exposure as categories, rather than numeric values, improving their interpret- ability and clinical relevance. We tested interactions of GDF-15 with imaging characteristics and lung function using similar models. Analyses were performed using Prism 6.0f (GraphPad Software, Inc; La Jolla, CA) and Stata v.12 (College Station, TX).
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Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood

Acute exacerbations of chronic obstructive pulmonary disease are associated with decreased CD4+ & CD8+ T cells and increased growth & differentiation factor-15 (GDF-15) in peripheral blood

key biomarker of cardiopulmonary stress, especially in- volving pulmonary vasculature. GDF-15 is a divergent TGF-beta superfamily member, first cloned from acti- vated macrophages [41] and named Macrophage inhibi- tory cytokine-1 (MIC-1). However, the same gene was cloned by other strategies, leading to many alternative names [42–45]. GDF-15 plays key regulatory roles in processes as diverse as cell cycle progression, differenti- ation, maintenance of pregnancy, apoptosis and tumor progression [46, 47]. Serum levels of GDF-15 levels rise modestly in acute coronary syndrome and congestive heart failure, in both conditions accurately predicting one-year mortality [48–50], but are very elevated in acute pulmonary embolus [51] and pulmonary hyperten- sion [52–54]. Elevated GDF-15 levels also predicted
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GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

GDF-15 is abundantly expressed in plexiform lesions in patients with pulmonary arterial hypertension and affects proliferation and apoptosis of pulmonary endothelial cells

GDF-15 is only weakly expressed in most tissues and organs [34]. It is therefore unsurprising that we only detected a weak immunostaining signal for GDF-15 in human normal lung tissue with almost no expression in the airways like bronchial and alveolar epithelial cells. As demonstrated in previous studies [18], GDF-15 was strongly expressed in alveolar macrophages which might indicate a role of this protein in innate immunity [2]. Interestingly, our immunostaining experiments clearly demonstrated strong expression of GDF-15 in the vascu- lar compartment of PAH patients, particularly in the intima of pulmonary arteries. GDF-15 staining was observed in pulmonary vessels of all sizes, beginning from the microvasculature up to large pulmonary ves- sels. The endothelial expression pattern was observed in normal lung as well as in lungs from PAH patients, sug- gesting a physiological role for GDF-15 in pulmonary endothelial cells. To date little is known about the func- tional role of GDF-15 in endothelial cells. A previous study demonstrated inhibitory effects of GDF-15 on pro- liferation, migration and invasion of endothelial cells in vitro as well as anti-angiogenic effects in vivo using a matrigel-plug-assay [11]. In contrast to these findings, a recently published paper demonstrated both angiogenic and anti-angiogenic properties of GDF-15 [12], which were concentration-dependent. GDF-15 elicited pro- angiogenic effects at low concentrations, whereas para- doxical effects were observed at higher concentrations (100 ng/ml). In accordance with this finding we too were able to demonstrate concentration-dependent pro- as well as anti-angiogenic effects of recombinant GDF- 15 protein on pulmonary endothelial cells in vitro. That different concentrations of a cytokine could result in dif- ferent cellular responses is well-known for members of the TGF- b -family. For instance, TGF- b 1 exerts bi-func- tional effects on endothelial cells, regarding activation, proliferation and migration. At low concentrations TGF- b 1 has a stimulating effect, whereas higher concentra- tions inhibit these processes [35]. It is challenging to speculate the active amount of GDF-15 in the pulmon- ary vasculature. However, addi-tional autocrine and paracrine pathways may determine the local concentra- tion of GDF-in the vascular compartment. Furthermore, a variety of activating or disabling regulators may inter- fere with the intra- and extracellular storage as well as the stability of GDF-15 in lung compartments.
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The Effect of Resistance Training on Serum Levels of NT-proBNP, GDF-15, and Markers of Cardiac Damage in the Elderly Males

The Effect of Resistance Training on Serum Levels of NT-proBNP, GDF-15, and Markers of Cardiac Damage in the Elderly Males

impairment of the function. CK-MB (creatine kinase-muscle/brain) isoenzyme is one of the most important markers of cardiac muscle damage. Totally, 15%-25% of CK in heart cells is as MB (CK-MB), while it is about 3% in skeletal muscles. The overall activity of CK and its isoenzymes is directly related to its bounding site (4). The total CK and CK-MM activities in the skeletal muscles are significantly higher than those of myocardium. While the CK-MB activity of the skeletal muscles is significantly less than that of the myocardium (5). Changes in the level of CK-MB is particularly useful to detect myocardial necrosis up to 48 hours after the onset of acute myocardial infarction (AMI) (6). Although CK-MB cytosolic enzyme is a marker to diagnose myocardial damage, it has diagnostic limitations. So that it increases after exercise and other events that are not related to the heart. Since CK-MB is not just specific to the heart, its increase may not indicate a cardiac damage (7). The total CK activity also increases following the intensive physical activities. After the muscle damage, total CK is released into the blood stream through the cell membrane (8). The levels of CK and CK-MB isozymes in the crowd of athletes or people who are working or suffering from muscle damage have been suspiciously observed (9). Several studies indicated the CK-MB as a marker of AMI in people with a history of exercise and reported that such histories can be considered as a major highlight point in the diagnosis. Weippert et al., (2016) studied the effect of intensive interval training on CK and CK-MB levels in young males. The results indicated a significant increase in the variables studied in all participants (10). However, release of CK-MB in the serum is of different origin and cannot be considered as the only marker for AMI diagnosis (11). Therefore, other markers such as NT-proBNP and GDF-15 should be considered in order to more accurately assess AMI and provide effective therapeutic strategies.
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GDF -15 and Severity Scores in Sickle Cell Disease Patients Attending Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

GDF -15 and Severity Scores in Sickle Cell Disease Patients Attending Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

In conclusion, the authors have found serum levels of GDF-15, which is an anti-inflammatory cytokine, to be increased in SCD compared to controls and to correlate negatively with disease severity. It may be a potential therapeutic target for intervention against ischaemia/reperfusion induced microvascular injury. Natural GDF-15 mimetic substances such as polyphenols found in Cassava (Manihot esculenta Crantz) leaves can potentially be explored as therapy for SCD. CONSENT AND ETHICAL APPROVAL

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GDF-15 protects from macrophage accumulation in a mousemodel of advanced atherosclerosis

GDF-15 protects from macrophage accumulation in a mousemodel of advanced atherosclerosis

There are several limitations to our study. Investigat- ing atherosclerotic lesions in LDLr −/− mice is mostly done in the aortic root, which is not a typical lesion lo- cation. It is known as a model of early stages in athero- sclerosis and does not show much progress in late-stage disease [30,31]. We did not focus on the onset of athero- sclerotic changes within the vascular wall such as lipid ac- cumulation in younger mice. Evaluation of fibrous caps was performed morphometrically as in many LDLr −/− mouse studies. Given the amount of tissue obtained, we were not able to stain for other parameters such as the dif- ferences in collagen content. Further, we do not know if bone-marrow transplantation has an effect on other cyto- kines, the immunosystem, or metabolism, which is an im- portant factor in atherosclerosis. Recently, it has been shown that GDF-15 is a key regulator in anorexia, and weight and fat loss [32]. However, lipid levels and body weight in our study were equally distributed. We could not detect any further change in lethality after transplantation.
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Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response

Identification of novel host biomarkers in plasma as candidates for the immunodiagnosis of tuberculosis disease and monitoring of tuberculosis treatment response

We investigated the diagnostic potentials of 74 host markers in plasma samples that were obtained from confirmed active TB cases and individuals with ORD, as candidates for the diagnosis of TB disease. Although 18 of the 74 host markers including relatively new biomarkers in the TB field namely; antithrombin III, GDF-15, NCAM, HCC1, MIP-4 and recently identified markers I-309, MIG, Apo A-1, transthyretin and CFH, showed potential in the diagnosis of TB disease, regardless of HIV infection status as determined by area under the ROC curve (AUC), the most optimal diagnostic biosignature irrespective of HIV infection status was a six-marker model comprising of NCAM, SAP, IL-1β, sCD40L, IL-13 and Apo A-1, which diagnosed TB disease with a sensitivity of 100% and specificity of 89.3%, with promising positive and negative predictive values. In the absence of HIV infection, six- marker biosignatures diagnosed TB disease with 100% accuracy.
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Plasma levels of heart failure biomarkers are primarily a reflection of extracardiac production

Plasma levels of heart failure biomarkers are primarily a reflection of extracardiac production

Figure 3. Cardiac function, remodeling and biomarker expression 4 and 8 weeks after TAC. (A) Representative MRI images of short axis in systole and diastole (upper panel). EF (%) 8 weeks after tLAD and pLAD, as determined by MRI. (B) Representative images of mid-ventricular slices stained with FITC-WGA to determine cell size (upper panels). Quantification of cell size based on FITC-WGA staining (lower panel). (C) NPPA gene expression (left panel), and NT-proANP biomarker plasma levels (right panel). (D-F) The same as (C), but for, respectively (D) LGALS3/Gal-3, (E) GDF-15 and (F) TIMP-1. All analysis N=15-20 for sham, N=8-10 per TAC group. Bars represent means. Error bars represent SEM. *P<0.05 versus control group. #P<0.05 versus TAC 4 wks. Red bar in (B) represents 50 µm.
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Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest

Growth differentiation factor 15 and early prognosis after out-of-hospital cardiac arrest

GDF-15 is a stress-responsive member of the transform- ing growth factor-β (TGF-β) cytokine superfamily. GDF- 15 is weakly expressed in tissues, including the central nervous system [21], under normal conditions. Although its pathobiology is not fully understood, it is strongly induced by macrophages in response to inflammation and tissue injury. Thus, circulating levels of GDF-15 have been identified as an inflammatory biomarker with prognostic value in several conditions, particularly in cardiovascular diseases. In the acute setting, increased levels are a robust predictor of organ dysfunction and death from acute myo- cardial infarction [6, 22, 23] to cardiogenic shock [24]. GDF-15 also serves as biomarker in other critical disease conditions, such as acute pulmonary embolism [25], acute respiratory distress syndrome [26], or sepsis [27]. On the other hand, at lower cut-off values, GDF-15 levels can pre- dict long-term cardiovascular events, bleeding, cancer, and all-cause mortality, both in patients with chronic heart dis- eases and in individuals that dwell in community settings
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Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease

Potential relation between soluble growth differentiation factor-15 and testosterone deficiency in male patients with coronary artery disease

In vitro, Kim et al. reported that the positive correlation between GDF-15 and C-reaction protein in a molecular level, which facilitated improved understanding of the pivotal inflammatory pathways important in CAD [20]. A recently published study observed an association of higher GDF-15 concentration with risk for mortality and heart failure in patients with CKD [21]. It indicated the association of GDF-15 with cardiac remodeling, which was the potentially important pathways in the patho- genesis of cardiovascular disease. Besides, serum GDF- 15 levels were in relation to disease severity [22] and elevated GDF-15 levels were helpful in classifying high- risk ACS patients who benefit from high-dose highly efficient statins [23], as well as predicting CV-death in a population of CAD patients after PCI [24]. And numer- ous studies [14] suggested that GDF-15 still added prog- nostic value to standard risk factors for predicting death, overall cardiovascular events, and provided additional information for risk stratification. All these data provide insight into the relationship between GDF-15 and CAD and supported that GDF-15 may be a specific marker for cardiovascular diseases, and this may be a particularly relevant pathway for inflammatory disease conditions such as CAD. Consistent with the previous studies, in our research, concentrations of GDF-15 in male patients with CAD were higher than controls, and GDF-15 levels increased with the severity of the disease.
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Original Article Downregulation of growth differentiation factor-15 in trichostatin A-induced apoptosis could play a role in progression of gastric cancer

Original Article Downregulation of growth differentiation factor-15 in trichostatin A-induced apoptosis could play a role in progression of gastric cancer

Abstract: Aim: To investigate the effect of trichostatin A (TSA) on gastric cancer cell line BGC-823, and identify the differentially expressed genes induced by TSA, which might participate in the progression of gastric cancer. Methods: MTT, fluorescence microscopy, and flow cytometry were used to detect the effect of TSA on growth inhibi- tion and apoptosis of BGC-823 cells. Using gene microarray, we analyzed the changes in gene expression. Change in growth differentiation factor-15 (GDF-15) was verified by qRT-PCR and Western blotting. The expression of GDF-15 in gastric cancer and adjacent normal tissues was detected by immunohistochemistry. Results: Apoptosis of BGC- 823 cells induced by TSA (75 ng/mL for 48 h) was demonstrated by flow cytometry. There were significant variations between TSA treated groups and control groups (P = 0.02). Nuclear chromatin condensation and fluorescence inten- sity were observed by fluorescence microscopy. GDF-15 gene expression and protein level were significantly reduced in the TSA treated group (75 ng/mL for 48 h). Immunohistochemistry demonstrated that the expression of GDF-15 in gastric adenocarcinoma was significantly higher than in the surrounding normal tissues (P < 0.05). Conclusion: Lower GDF-15 gene expression due to TSA-induced apoptosis was found in gastric cancer cell line BGC-823. Higher GDF-15 gene expression was seen in gastric adenocarcinoma tissues.
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Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study

Determinants of growth differentiation factor 15 in patients with stable and acute coronary artery disease. A prospective observational study

in patients with high risk NSTEMI [5]. In patients with STEMI a recent sub-study of the PLATO trial showed predictive impact of admission GDF-15 for future spon- taneous MI and death [32]. A further analysis of the PLATO trial evidenced a predictive role for GDF-15 in patients with ASC undergoing, but not in those without invasive management [33]. Similarly in STEMI patients who underwent medical reperfusion therapy, GDF-15 levels were predictive of worse prognosis [2]. Wollert et al. found in a sub-investigation of the GUSTO IV trial that GDF-15 was a strong predictor of composite end- point of death and MI [6]. However in that study the predictive power for the combined endpoint was mainly driven by the endpoint death and not MI [6]. Similar to those investigations, we found GDF-15 measured before coronary intervention in patients with CAD in stable and acute setting is a powerful predictor for death. However, GDF-15 was proven not predictive of combined ischemic endpoints of (non-fatal MI, UA, unplanned revasculariza- tion, ST, TIA and stroke). The main differences occurred in our vs. previous investigations could be explained by the fact that we investigated CAD patients  in chronic as well as acute setting undergoing revascularization via PCI (PCI performed in 100  % of the study popula- tion) compared to earlier studies performed by Wollert and Kempf [2, 6] In those investigations patients were treated with thrombolytics or in less frequency received
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Preoperative plasma growth differentiation factor 15 for prediction of acute kidney injury in patients undergoing cardiac surgery

Preoperative plasma growth differentiation factor 15 for prediction of acute kidney injury in patients undergoing cardiac surgery

Results: There were 258 patients (21.9 %) with AKI (AKI stage 1 (AKI-1), n = 175 (14.9 %); AKI-2, n = 6 (0.5 %); AKI-3, n = 77 (6.5 %)). The incidence of AKI-1 and AKI-3 increased significantly from the lowest to the highest tertiles of GDF-15. In logistic regression, preoperative GDF-15, additive Euroscore, age, plasma creatinine, diabetes mellitus, and duration of cardiopulmonary bypass were independently associated with AKI. Inclusion of GDF-15 in a logistic regression model comprising these variables significantly increased the area under the curve (AUC 0.738 without and 0.750 with GDF-15 included) and the net reclassification ability to predict AKI. Comparably, in receiver operating characteristic analysis the predictive capacity of the CC-ARF score (AUC 0.628) was improved by adding GDF-15 (AUC 0.684) but this score also had lower predictability than the logistic regression model. In random forest analyses the predictive capacity of GDF-15 was especially pronounced in patients with normal plasma creatinine. Conclusion: This suggests that preoperative plasma GDF-15 independently predicts postoperative AKI in patients undergoing elective cardiac surgery and is particularly helpful for risk stratification in patients with normal creatinine. Trial registration: NCT01166360 on July 20, 2010.
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A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases

A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases

We used Mann-Whitney U and Kruskal-Wallis nonparametric testing to determine statistical differences between groups. We calculated the diagnostic sensitivity and the corresponding 95% confidence intervals. An unadjusted diagnostic OR was determined for comparison with FGF-21. Receiver operating characteristic (ROC) curves were plotted using sensitivity vs 100 2 specificity on a continuous scale and the area under the curve (AUC) was used to determine the relative diagnostic capacity. Biomarker levels were correlated with other biochemical measurements and clinical assess- ment tools using nonparametric Spearman correlation testing. Lin- ear regression analysis was used to determine if statistically correlated parameters could predict GDF-15 concentration. Mul- tivariate linear regression analysis was performed to determine fac- tors capable of predicting disease while controlling for confounders that may influence serum GDF-15 concentration.
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Serum Growth Differentiation Factor 15 in Patients with Ulcerative Colitis

Serum Growth Differentiation Factor 15 in Patients with Ulcerative Colitis

Recent evidence has, however, shown conflicting results on the physiological and pathophysiological role of GDF-15 as an erythroid regulator of hepcidin, both in humans and mice. For example, a significant increase in serum GDF-15 was not observed in human volunteers who received erythropoietin or in volunteers who underwent phlebotomy. In both these cases, an erythropoietic drive was present and hepcidin levels were found to be decreased but these did not correlate with serum GDF-15 levels (Ashby et al. 2010). GDF-15 knock-out mice did not show any significant effect on hematological parameters in these mice. Their response to phlebotomy, with respect to iron parameters, was similar to that in wild type mice (Casanovas et al. 2013). This suggested that GDF-15 may not be an important erythroid regulator in mice during normal erythropoiesis.
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Growth differentiation factor-15 is associated with cardiovascular outcomes in patients with coronary artery disease

Growth differentiation factor-15 is associated with cardiovascular outcomes in patients with coronary artery disease

In this study, we found that GDF-15 concentra- tions higher than 1800  ng/L were associated with an increased risk of all-cause death and MACEs in patients with established CAD. After adjusting for both estab- lished risk factors for CV disease and these other prog- nostic biomarkers, GDF-15 remained an independent indicator of MACEs and all-cause death (Fig.  6). Even more, we observed that GDF-15 provided an incre- mental prognostic value beyond a clinical model for MACEs and all-cause death. Besides, our research added new evidence for the short-term predictive value of GDF-15 for CAD patients. Finally, higher GDF-15 concentrations in the setting of established CAD were consistently related with an increased prevalence of cardiovascular risk factors, the result is in consistent with previous studies [16]. Our results provide updated information on the short-term and long-term prognos- tic role of GDF-15 in CAD, our result indicates that the addition of plasma GDF-15 measurements to informa- tion from clinical characteristics and established CV risk factors might further improve risk stratification.
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Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo

Growth differentiation factor-15 is associated with muscle mass in chronic obstructive pulmonary disease and promotes muscle wasting in vivo

sociated with exercise capacity in both patient cohorts. COPD patients show a fi bre shift from a predominance of type I fi bres to a predominance of type IIA fi bres in the quadriceps muscle, and this change in fi bre proportion is associated with a marked reduction in exercise capacity. 38 However, GDF-15 expression was not associated with fi bre type within the muscle nor was there an association of serum GDF-15 with fi bre proportion. These data indicate that an increase in type II fi bre proportion is not the main cause for the increase in GDF-15 expression observed and that any effect of circulating GDF-15 on fi bre proportion is not a signi fi cant contributor to the muscle fi bre propor- tions in COPD patients. Consistent with this suggestion, the mouse model did not show an equivalent fi bre shift but showed a trend towards a reduction in the expression of all MHCs. However, the fi bre pro fi le of the murine tibialis anterior is predominantly type IIX and type IIB fi bres so that any shift towards a more glycolytic pro fi le may be hard to identify.
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