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Proteomic screening of glycoproteins in human plasma for frailty biomarkers.

ABSTRACT: The application of proteomics methodology for analyzing human blood samples is of increasing importance as a noninvasive method for understanding, detecting, and monitoring disease. In particular, glycoproteomic analysis may be useful in the study of age-related diseases and syndromes, such as frailty. This study demonstrates the use of methodology for isolating plasma glycoproteins using lectins, comparing the glycoproteome by frailty status using two-dimensional polyacrylamide gel electrophoresis and identifying glycoproteins using mass spectrometry. In a pilot study, we found seven glycoproteins to differ by at least twofold in prefrail compared with nonfrail older adults, including haptoglobin, transferrin, and fibrinogen, consistent with known inflammatory and hematologic changes associated with frailty. Enzyme-linked immunosorbent assay analysis found that plasma transferrin concentration was increased in frail and prefrail older adults compared with nonfrail, confirming our proteomic findings. This work provides evidence for using a reproducible methodology for conducting clinical proteomic comparative studies of age-related diseases.

SUBMITTER: Shamsi KS

PROVIDER: S-EPMC3403859 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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Proteomic screening of glycoproteins in human plasma for frailty biomarkers.

Shamsi Kinza S KS Pierce Anson A Ashton Aaron S AS Halade Dipti G DG Richardson Arlan A Espinoza Sara E SE

The journals of gerontology. Series A, Biological sciences and medical sciences 20120104 8

The application of proteomics methodology for analyzing human blood samples is of increasing importance as a noninvasive method for understanding, detecting, and monitoring disease. In particular, glycoproteomic analysis may be useful in the study of age-related diseases and syndromes, such as frailty. This study demonstrates the use of methodology for isolating plasma glycoproteins using lectins, comparing the glycoproteome by frailty status using two-dimensional polyacrylamide gel electrophore ...[more]

PMID: 22219522

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Project description:Proteomic approaches have unique advantages in the identification of biological pathways that influence physical frailty, a multifactorial geriatric syndrome predictive of adverse health outcomes in older adults. To date, proteomic studies of frailty are scarce, and few evaluated prefrailty as a separate state or examined predictors of incident frailty. Using plasma proteins measured by 4955 SOMAmers in the Atherosclerosis Risk in Community study, we identified 134 and 179 proteins cross-sectionally associated with prefrailty and frailty, respectively, after Bonferroni correction (p < 1 × 10-5 ) among 3838 older adults aged ≥65 years, adjusting for demographic and physiologic factors and chronic diseases. Among them, 23 (17%) and 82 (46%) were replicated in the Cardiovascular Health Study using the same models (FDR p < 0.05). Notably, higher odds of prefrailty and frailty were observed with higher levels of growth differentiation factor 15 (GDF15; pprefrailty = 1 × 10-15 , pfrailty = 2 × 10-19 ), transgelin (TAGLN; pprefrailty = 2 × 10-12 , pfrailty = 6 × 10-22 ), and insulin-like growth factor-binding protein 2 (IGFBP2; pprefrailty = 5 × 10-15 , pfrailty = 1 × 10-15 ) and with a lower level of growth hormone receptor (GHR, pprefrailty = 3 × 10-16 , pfrailty = 2 × 10-18 ). Longitudinally, we identified 4 proteins associated with incident frailty (p < 1 × 10-5 ). Higher levels of triggering receptor expressed on myeloid cells 1 (TREM1), TAGLN, and heart and adipocyte fatty-acid binding proteins predicted incident frailty. Differentially regulated proteins were enriched in pathways and upstream regulators related to lipid metabolism, angiogenesis, inflammation, and cell senescence. Our findings provide a set of plasma proteins and biological mechanisms that were dysregulated in both the prodromal and the clinical stage of frailty, offering new insights into frailty etiology and targets for intervention.

Dataset Information

Proteomic screening of glycoproteins in human plasma for frailty biomarkers.

Publications

Proteomic screening of glycoproteins in human plasma for frailty biomarkers.

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