Targeted Approach to Distinguish and Determine Absolute Levels of GDF8 and GDF11 in Mouse Serum

Camparini, Luca; Kollipara, Laxmikanth; Sinagra, Gianfranco; Loffredo, Francesco; Sickmann, Albert; Shevchuk, Olga

doi:10.1002/pmic.201900104

Cited by 7 publications

(5 citation statements)

References 14 publications

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“…Their results were partially confirmed by the SomaScan aptamer technology measurement of samples from two large cohort studies in which, however, sarcopenia was not assessed [ 110 ]. Further research investigated various, specific myostatin measurement methods, such as immunoassays, immunoradiometric sandwich assay, antibody-free assay and liquid chromatography-tandem mass spectrometry assay combined with immunoprecipitation [ 111 , 112 , 113 , 114 ]. These new, specific assays could be used to clarify discrepancies in earlier results, as well as serve as a validation tool for commercially available methods.…”

Section: Myostatin and Muscle Wastingmentioning

confidence: 99%

Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

2020

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Sarcopenia is a geriatric syndrome with a significant impact on older patients’ quality of life, morbidity and mortality. Despite the new available criteria, its early diagnosis remains difficult, highlighting the necessity of looking for a valid muscle wasting biomarker. Myostatin, a muscle mass negative regulator, is one of the potential candidates. The aim of this work is to point out various factors affecting the potential of myostatin as a biomarker of muscle wasting. Based on the literature review, we can say that recent studies produced conflicting results and revealed a number of potential confounding factors influencing their use in sarcopenia diagnosing. These factors include physiological variables (such as age, sex and physical activity) as well as a variety of disorders (including heart failure, metabolic syndrome, kidney failure and inflammatory diseases) and differences in laboratory measurement methodology. Our conclusion is that although myostatin alone might not prove to be a feasible biomarker, it could become an important part of a recently proposed panel of muscle wasting biomarkers. However, a thorough understanding of the interrelationship of these markers, as well as establishing a valid measurement methodology for myostatin and revising current research data in the light of new criteria of sarcopenia, is needed.

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Section: Myostatin and Muscle Wastingmentioning

confidence: 99%

Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

2020

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“…Second, LC-MS/MS was used to quantify serum GDF11 and myostatin levels. This technique is highly specific and more sensitive for distinguishing between GDF11 and myostatin than antibody-based methods ( Semba et al 2019 ; Camparini et al 2020 ), yet it provides only one aspect of a more complex system. For example, these proteins may circulate freely in the active form or may be bound to inhibitor proteins, such as GASP-1 and GASP-2 ( Lee and Lee 2013 ), which render them inactive.…”

Section: Resultsmentioning

confidence: 99%

A systems approach using Diversity Outbred mice distinguishes the cardiovascular effects and genetics of circulating GDF11 from those of its homolog, myostatin

Starcher

Peissig

Stanton

et al. 2021

G3 Genes|Genomes|Genetics

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Growth differentiation factor 11 (GDF11) is a member of the TGF-β protein family that has been implicated in the development of cardiac hypertrophy. While some studies have suggested that systemic GDF11 protects against cardiomyocyte enlargement and left ventricular wall thickening, there remains uncertainty about the true impact of GDF11 and whether its purported effects are actually attributable to its homolog myostatin. The present study was conducted to resolve the statistical and genetic relationships among GDF11, myostatin, and cardiac hypertrophy in a mouse model of human genetics, the Diversity Outbred (DO) stock. In the DO population, serum GDF11 concentrations positively correlated with cardiomyocyte cross sectional area, while circulating myostatin levels were negatively correlated with body weight, heart weight, and left ventricular wall thickness and mass. Genetic analyses revealed that serum GDF11 concentrations are modestly heritable (0.23) and identified a suggestive peak on murine chromosome 3 in close proximity to the gene Hey1, a transcriptional repressor. Bioinformatic analyses located putative binding sites for the HEY1 protein upstream of the Gdf11 gene in the mouse and human genomes. In contrast, serum myostatin concentrations were more heritable (0.57) than GDF11 concentrations, and mapping identified a significant locus near the gene FoxO1, which has binding motifs within the promoter regions of human and mouse myostatin genes. Together, these findings more precisely define the independent cardiovascular effects of GDF11 and myostatin, as well as their distinct regulatory pathways. Hey1 is a compelling candidate for the regulation of GDF11 and will be further evaluated in future studies.

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“…Proteomic studies have also addressed the kilometres of vascular beds and extracellular matrix responsible for transporting blood, giving valuable insights into the molecular anatomy of aneurysms and atherosclerosis 126 , 127 . Targeted MS methods have been developed, again especially where interferences obfuscate immunoassays 128 or where additional biological context is required 129 . Likewise, volumetric absorptive micro-sampling VAMS blood collection devices (e.g., Mitra devices or dried blood spots) allow patients to mail samples from home to analytical labs to undertake SRM/MRM/PRM assays quantifying CVD risk-associated apolipoproteins 130 or other markers 131 .…”

Section: Translating Proteomics To Precision Medicinementioning

confidence: 99%

A high-stringency blueprint of the human proteome

et al. 2020

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The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP’s tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.

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Targeted Approach to Distinguish and Determine Absolute Levels of GDF8 and GDF11 in Mouse Serum

Cited by 7 publications

References 14 publications

Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

Myostatin as a Biomarker of Muscle Wasting and other Pathologies-State of the Art and Knowledge Gaps

A systems approach using Diversity Outbred mice distinguishes the cardiovascular effects and genetics of circulating GDF11 from those of its homolog, myostatin

A high-stringency blueprint of the human proteome

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