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Use of biglycan in the assessment of heart failure

A heart failure, proteoglycan technology, applied in the field of the application of biglycan in the assessment of heart failure, can solve the problem of insufficient single marker

Inactive Publication Date: 2011-09-14
F HOFFMANN LA ROCHE & CO AG +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0032] However, as for many other diagnostic fields, a single marker is not sufficient

Method used

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  • Use of biglycan in the assessment of heart failure
  • Use of biglycan in the assessment of heart failure
  • Use of biglycan in the assessment of heart failure

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0179] Mouse Model of Heart Failure

[0180] 1.1 R9C mouse model

[0181] Hereditary human dilated cardiomyopathy has been reported to arise from an Arg9 to Cys transition in the human phospholamban (PLN) gene (PLN-R9C) (Schmitt, J.P. et al., Science 299 (2003) 1410-1413). Onset of dilated cardiomyopathy in affected patients generally begins during adolescence, followed by progressive deterioration of cardiac function, leading to crisis and death. Transgenic mouse models of this mutation display a similar cardiac phenotype to affected patients with dilated cardiomyopathy, reduced cardiac contractility, and premature death (Schmitt et al., 2003, supra).

[0182] We determined survival curves for transgenic mice. PLN-R9C mice had a median survival of only ~20 weeks, of which less than 15% persisted through 24 weeks ( Figure 1A ). The first recorded death in the PLN-R9C line was observed at 12 weeks of age, whereas only one wild-type control mouse died over the 24 week perio...

Embodiment 2

[0196] microarray analysis

[0197] Crude tissue preparations are used for microarray analysis without further isolation of organelles. Microarray data analysis methods are described in the literature (see, eg, US 5,807,522; Robinson, W.H. et al., Nat. Med. 8 (2002) 295-301; Robinson, W.H. et al., Arthritis Rheum. 46 (2002) 885- 893).

[0198] Sample preparation and mass spectrometry

[0199] Cardiac homogenization and organelle isolation

[0200] The heart was isolated, the atria were removed, and the ventricles were carefully minced with a razor blade and washed extensively with ice-cold PBS (phosphate-buffered saline) to remove excess blood. Using a loose-fitting hand-held glass homogenizer, dissolve the tissue in 10 ml of lysis buffer (250 mM sucrose, 50 mM Tris-HCl pH 7.6, 1 mM MgCl2, 1 mM DDT (dithiothreitol), and 1 mM PMSF ( phenylmethylsulfonyl fluoride) for 30 s. All subsequent steps were performed at 4 °C. The lysate was centrifuged at 800 x g for 15 min in a ben...

Embodiment 3

[0209] Statistical evaluation of data obtained in model systems

[0210] 3.1 Statistical methods used to generate differentially expressed p-values ​​for the R9C mouse model

[0211] The raw data, obtained with the method described in Example 2, consisted of 6190 proteins each with a count of the spectra, the sum of all spectra associated with the protein, for each run 137 different experiments. Population normalization was performed on the raw data 6190 protein subsets, which first split the data in each run into equal groups, set to 100 for our analysis, based on their spectral counts. LOESS (Cleveland, W.S. and Devlin, S.J., Journal of the American Statistical Association 83 (1988) 596-610) was subsequently performed on each group (1 – 100), adjusting the spectral counts across groups of genes with similar spectral counts difference.

[0212] Based on our raw data, we constructed 2 linear models, the first using control / disease, time (8W, 16W, end) and location (cyto, mic...

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Abstract

The invention relates to a method for assessing heart failure in vitro comprising the steps of measuring in a sample the concentration of the marker biglycan, of optionally measuring in the sample the concentration of one or more other marker(s) of heart failure, and of assessing heart failure by comparing the concentration determined in for biglycan and the concentration(s) determined for the optionally one or more other marker to the concentration of this marker or these markers as established in a reference population. Also disclosed are the use of biglycan as a marker protein in the assessment of heart failure, a marker combination comprising biglycan and a kit for measuring biglycan.

Description

technical field [0001] The present invention relates to a method for assessing heart failure in an individual comprising the steps of: a) measuring the concentration of the labeled biglycan in a sample obtained from the individual, b) optionally measuring a The concentration of one or more other markers of heart failure, and by comparing the concentration determined in step (a) and optionally the concentration determined in step (b) with the concentration of such marker or markers as determined in the control sample comparison to assess heart failure. Also disclosed are the use of biglycan as a marker protein in the assessment of heart failure, marker combinations comprising biglycan, and kits for measuring biglycan. Background technique [0002] Heart failure (HF) is a major and growing public health problem. In the US for example about 5 million patients suffer from HF, and more than 550,000 patients are diagnosed with HF for the first time each year (see: American Heart...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/68
CPCG01N2333/4722G01N33/6893G01N2800/325
Inventor U-H·韦恩许斯-特伦S·阿拉布D·布洛克A·埃米利A·格拉莫利尼G·赫斯H·许迪希P·刘D·麦克莱南
Owner F HOFFMANN LA ROCHE & CO AG
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