Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes

Zierfuss, Bernhard; Höbaus, Clemens; Herz, Carsten Thilo; Pesau, Gerfried; Koppensteiner, Renate; Schernthaner, Gerit‐Holger

doi:10.1007/s00380-019-01453-7

Cited by 15 publications

(9 citation statements)

References 38 publications

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“…MDCF-2 elicits a concerted change in WLZ-associated proteins, a number of which are effectors of bone growth and skeletal muscle development. Some of these proteins have also been implicated in metabolic disorders( 24 – 30 ). However, augmenting growth of bone and skeletal muscle may promote a rebalancing of the rapid ‘catch-up’ fat accretion, observed when undernourished children are given standard nutritional interventions, towards a more appropriate lean-to-fat mass ratio, simultaneously improving growth and protecting from later obesity( 31 , 32 ).…”

Section: Discussionmentioning

confidence: 99%

A Microbiota-Directed Food Intervention for Undernourished Children

et al. 2021

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BACKGROUND More than 30 million children worldwide suffer from moderate acute malnutrition (MAM). Current treatments have limited effectiveness and much remains unknown about pathogenesis. Children with MAM exhibit perturbed development of their gut microbiota. METHODS Slum-dwelling Bangladeshi children, aged 12 to 18 months, with moderate acute malnutrition (n=124) received a microbiota-directed complementary food (MDCF-2) or an existing ready-to-use supplementary food (RUSF), twice daily for three months followed by a 1-month period of monitoring. We obtained weight-for-length, weight-for-age, and length-for-age Z-scores and mid-upper arm circumference at baseline and fortnightly, through four months. We compared the rate of change of these related phenotypes between baseline and three months, and between baseline and four months. We also measured levels of 4,977 proteins in plasma plus 209 bacterial taxa in fecal samples. RESULTS 118 children completed the intervention (n=59/arm). The rate of change in weight-for-length Z-score (β-WLZ), weight-for-age Z-score, and mid upper arm circumference is consistent with a benefit of MDCF-2 on growth over the course of the study including the one-month follow-up. Receipt of MDCF-2 was linked to the magnitude of change in levels of 70 β-WLZ-positively correlated plasma proteins including mediators of bone growth, neurodevelopment and inflammation (gene set enrichment analysis [GSEA];p<0.001) and the abundances of 23 WLZ-associated bacterial taxa (GSEA;p<0.001). CONCLUSIONS These findings provide support for further clinical investigation of MDCF-2 as a dietary supplement for young children with MAM and provide insight into mechanisms by which this targeted manipulation of microbiota components may be linked to growth. (Supported by the Bill and Melinda Gates Foundation and the NIH; ClinicalTrials.gov identifier: NCT04015999 )

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Section: Discussionmentioning

confidence: 99%

A Microbiota-Directed Food Intervention for Undernourished Children

et al. 2021

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“…In contrast to the rest molecules of the thrombospondin family, TSP-4 promotes angiogenesis (36,37). Recently, Zierfuss et al found increased levels of TSP-4 in T2DM patients with peripheral arterial disease suggesting that microvascular angiogenesis promoted in diabetes is associated with the overexpression of TSP-4 (38).…”

Section: Discussionmentioning

confidence: 99%

Quantitative Comparative Proteomics Reveals Candidate Biomarkers for the Early Prediction of Gestational Diabetes Mellitus: A Preliminary Study

Mavreli

Evangelinakis

Παπαντωνίου

et al. 2020

In Vivo

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Aim: To identify differentially expressed proteins (DEPs) in 1 st trimester maternal plasma between pregnant women at risk for gestational diabetes mellitus (GDM) and uncomplicated controls. Materials and Methods: Firsttrimester plasma from five women who developed GDM and five from non-diabetic ones were analyzed using isobaric tag for relative and absolute quantitation -labeled proteomics. Enzyme-linked immunosorbent assay was further applied in an independent cohort of 25 GDM cases and 25 controls for verification. Results: Prenylcysteine oxidase 1 (PCYOX1), beta-ala-his dipeptidase (CNDP1), extracellular matrix protein 1 (ECM1), basement membrane-specific heparan sulfate proteoglycan core protein (HSPG2), thrombospondin-4 (TSP-4) demonstrated significant differences in expression between the two groups (p<0.05). DEPs are mainly associated with complement and coagulation cascades. Conclusion: The reported plasma proteomic changes represent potential biomarkers for the early identification of women at risk for GDM. Future studies using larger and more diverse cohorts are necessary to assess the clinical utility of these findings.

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“…For instance, serum high mobility group box (HMGB) 1, fibroblast growth factor (FGF) 23 and osteopontin (OPN) have been correlated with the presence of PAD [ 24 , 25 ]. In addition, thrombospondin-4 (TSP-4) levels were significantly increased with PAD severity in patients with concomitant diabetes and could be a novel marker of atherosclerotic activity [ 26 ]. Recently, the association between circulating serum growth differentiation factor (GDF) 15 and lower extremity atherosclerotic disease (LEAD) has been investigated in Chinese diabetes subjects [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Association of serum Cyr61 levels with peripheral arterial disease in subjects with type 2 diabetes

Feng

Sun

et al. 2020

Cardiovasc Diabetol

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Background The prevalence of peripheral artery disease (PAD) is obviously increased in patients with diabetes. Existing evidence shows that cysteine-rich angiogenic inducer 61 (Cyr61), a 40-kD secreted protein, plays important roles in regulating cellular physiological processes. Recent studies have demonstrated a significant correlation between serum Cyr61 and atherosclerosis. However, the relationship between Cyr61 levels and PAD in patients with type 2 diabetes (T2DM) remains obscure. Methods Data from a total of 306 subjects with T2DM were cross-sectionally analysed. The extent of PAD was determined by using the Fontaine classification, which defines four stages. We measured serum Cyr61 concentrations by ELISA in subjects with and without PAD at Fontaine’s stage II, III, or IV. Logistic regression models were used to examine the independent association of Cyr61 with PAD. Results Out of the 306 subjects enrolled, 150 were free from PAD, while 156 had clinically significant PAD. In subjects with PAD, the prevalences of Fontaine classification stages II, III and IV were 48.7%, 32.1%, and 19.2%, respectively. Patients with more advanced PAD had significantly higher Cyr61 (P for trend < 0.001). The prevalence of PAD on the basis of severity increased with increasing Cyr61 quartiles (all P values for trends < 0.001), and the severity of PAD was positively correlated with Cyr61 quartiles (r = 0.227, P = 0.006). The association of Cyr61 levels with PAD remained after adjusting for major risk factors in a logistic regression analysis. Conclusions Our results demonstrated that Cyr61 was significantly increased in PAD patients with T2DM and that Cyr61 levels were positively associated with disease severity. Cyr61 could be a promising biomarker and further studies are needed to assess its clinical utility.

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Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes

Cited by 15 publications

References 38 publications

A Microbiota-Directed Food Intervention for Undernourished Children

A Microbiota-Directed Food Intervention for Undernourished Children

Quantitative Comparative Proteomics Reveals Candidate Biomarkers for the Early Prediction of Gestational Diabetes Mellitus: A Preliminary Study

Association of serum Cyr61 levels with peripheral arterial disease in subjects with type 2 diabetes

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