Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

Szulc, Paweł; Hofbauer, Lorenz C.; Rauner, Martina; Goettsch, Claudia; Chapurlat, Roland; Schoppet, Michael

doi:10.1530/eje-12-0512

Cited by 14 publications

(7 citation statements)

References 51 publications

(67 reference statements)

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“…Indeed, in contrast to early observations highlighting a link between elevated levels of Mstn and low muscularity situations, [41][42][43] recent studies showed a decrease of circulating Myostatin in conditions characterized by reduced skeletal muscle mass such as ageing, but without correlation between Myostatin levels and muscle mass. [44][45][46] In agreement with our results, Breitbart et al observed in cancer patients with body weight loss a decrease of circulating Myostatin propeptide levels, reflecting a decrease of Myostatin production. 47 The lack of consistency between these studies might be explained by the use of various immunoassays detecting different forms of Myostatin and a possible cross-reactivity with other TGFβ members.…”

Section: Discussionsupporting

confidence: 93%

“…Although Myostatin is doubtless an inhibitor of skeletal muscle mass development, its role in muscle atrophy remains unclear. Indeed, in contrast to early observations highlighting a link between elevated levels of Mstn and low muscularity situations,41, 42, 43 recent studies showed a decrease of circulating Myostatin in conditions characterized by reduced skeletal muscle mass such as ageing, but without correlation between Myostatin levels and muscle mass 44, 45, 46. In agreement with our results, Breitbart et al .…”

Section: Discussionsupporting

confidence: 89%

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Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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BackgroundSeveral experimental evidences pinpoint the possible role of Activin A (ActA) as a driver of cancer cachexia. Supporting this hypothesis, we showed recently that human cancer cachexia is associated with high ActA levels. Moreover, ActA levels were correlated with body weight loss and skeletal muscle density, two prognostic factors in cancer patients. Our goal was therefore to investigate the value of ActA to predict survival in cancer patients.MethodsPatients with colorectal or lung cancer were prospectively enrolled at the time of diagnosis or relapse between January 2012 and March 2014. At baseline, patients had clinical, nutritional, and functional assessment. Body composition and skeletal muscle density were measured by CT scan, and plasma ActA concentrations were determined. Overall survival (OS) was analysed since inclusion to 24 months later.ResultsSurvival data were available for 149 patients out of 152. Patients with high ActA (≥408 pg/mL) had lower OS than those with low levels, regardless the type of cancer (OS in colorectal cancer, 50% vs. 79%, P < 0.05; and in lung cancer, 27% vs. 67%, P = 0.001). The multivariable analysis confirmed the prognostic value of ActA independently of tumour stage or inflammatory markers, particularly in lung cancer. Low muscularity was also an independent prognostic factor.ConclusionsOur study demonstrates that high ActA level is an independent prognosis factor of survival in cancer patients. More than a basic marker of the severity of the neoplastic disease or of the inflammatory process, ActA seems to influence survival by contributing to the development of cachexia and loss of skeletal muscle mass.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 89%

Circulating Activin A predicts survival in cancer patients

Loumaye

Barsy

Nachit

et al. 2017

J cachexia sarcopenia muscle

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“…Similar results were reported in the STRAMBO study, which investigated in a large cohort of healthy men the association between serum levels of Mstn and abdominal aortic calcifications evaluated through spine dual-energy X-ray absorptiometry. In this case, the authors confirmed that, at least in older men, total Mstn serum levels were inversely correlated with vascular calcifications [98].…”

Section: Myostatin and Vascular Calcificationsupporting

confidence: 69%

Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification

Esposito

Verzola

Picciotto

et al. 2021

Cells

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A current hypothesis is that transforming growth factor-β signaling ligands, such as activin-A and myostatin, play a role in vascular damage in atherosclerosis and chronic kidney disease (CKD). Myostatin and activin-A bind with different affinity the activin receptors (type I or II), activating distinct intracellular signaling pathways and finally leading to modulation of gene expression. Myostatin and activin-A are expressed by different cell types and tissues, including muscle, kidney, reproductive system, immune cells, heart, and vessels, where they exert pleiotropic effects. In arterial vessels, experimental evidence indicates that myostatin may mostly promote vascular inflammation and premature aging, while activin-A is involved in the pathogenesis of vascular calcification and CKD-related mineral bone disorders. In this review, we discuss novel insights into the biology and physiology of the role played by myostatin and activin in the vascular wall, focusing on the experimental and clinical data, which suggest the involvement of these molecules in vascular remodeling and calcification processes. Moreover, we describe the strategies that have been used to modulate the activin downward signal. Understanding the role of myostatin/activin signaling in vascular disease and bone metabolism may provide novel therapeutic opportunities to improve the treatment of conditions still associated with high morbidity and mortality.

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“…Patients with high myostatin levels had lower AAC scores than did those with low myostatin levels, indicating potentially favorable effects on VC in dialysis patients. Szulc et al [10] reported previously in the Structure of the Aging Men’s Bones (STRAMBO) study that older males with AAC have lower myostatin levels than those without AAC. Generally, the expression of myostatin and the severity of vascular damage show a positive correlation.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have shown that the abdominal aortic calcification (AAC) score on plain radiography has a very good correlation with the identification of coronary artery calcification and low bone mass, which are risk factors for mortality [8,9]. A previous human study reported that serum myostatin levels were negatively associated with AAC in older males [10]. However, no research has been conducted on the relationship between myostatin levels and AAC in dialysis patients at this time, to our knowledge.…”

Section: Introductionmentioning

confidence: 99%

Serum myostatin levels are associated with abdominal aortic calcification in dialysis patients

Lee

Kim

Lee³

et al. 2019

Kidney Res Clin Pract

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BackgroundSerum myostatin levels are increased according to renal function decline and myostatin may be a main mediator of chronic kidney disease–related sarcopenia. A previous study reported that serum myostatin level was negatively associated with abdominal aortic calcification (AAC) in older males. The aim of this study was to assess the association between serum myostatin level and AAC among dialysis patients of both sexes. In addition, we analyzed the relationship between serum myostatin level, muscle mass, and bone mineral density (BMD).MethodsIn this cross-sectional study, we evaluated AAC in the lateral lumbar spine using plain radiography and BMD in 71 patients undergoing dialysis. We classified patients into two groups according to the median value of myostatin as follows: those with high myostatin levels (≥ 5.0 ng/mL) and those with low myostatin levels (< 5.0 ng/mL).ResultsThe proportion of patients with an AAC score of five points or more was higher among those with low myostatin levels. Myostatin level was negatively associated with AAC scores on plain radiography and had a positive association with skeletal muscle mass and T-scores for BMD measured at the total hip and femur neck. Lower myostatin levels were independently associated with higher AAC scores following adjustment for age, sex, diabetes mellitus, dialysis vintage, dialysis modality, and osteoprotegerin level.ConclusionLower serum myostatin levels were associated with higher AAC scores, lower muscle mass, and lower BMD in dialysis patients. Further, prospective studies and those with larger cohorts are necessary to validate these findings.

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Serum myostatin levels are negatively associated with abdominal aortic calcification in older men: the STRAMBO study

Cited by 14 publications

References 51 publications

Circulating Activin A predicts survival in cancer patients

Circulating Activin A predicts survival in cancer patients

Myostatin/Activin-A Signaling in the Vessel Wall and Vascular Calcification

Serum myostatin levels are associated with abdominal aortic calcification in dialysis patients

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