Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
von zur Muhlen, C; Schiffer, E; Sackmann, C; Zürbig, P; Neudorfer, I; Zirlik, A; Htun, N; Iphöfer, A; Jänsch, L; Mischak, H; Bode, C; Chen, YC; Peter, K.
Urine proteome analysis reflects atherosclerotic disease in an ApoE-/- mouse model and allows the discovery of new candidate biomarkers in mouse and human atherosclerosis.
MOL CELL PROTEOMICS. 2012; 11(7): M111.013847-M111.013847.
Doi: 10.1074/mcp.M111.013847
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- Co-Autor*innen der Med Uni Graz
- Zirlik Andreas
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- Abstract:
- Noninvasive diagnosis of atherosclerosis via single biomarkers has been attempted but remains elusive. However, a previous polymarker or pattern approach of urine polypeptides in humans reflected coronary artery disease with high accuracy. The aim of the current study is to use urine proteomics in ApoE(-/-) mice to discover proteins with pathophysiological roles in atherogenesis and to identify urinary polypeptide patterns reflecting early stages of atherosclerosis. Urine of ApoE(-/-) mice either on high fat diet (HFD) or chow diet was collected over 12 weeks; urine of wild type mice on HFD was used to exclude diet-related proteome changes. Capillary electrophoresis coupled to mass spectrometry (CE-MS) of samples identified 16 polypeptides specific for ApoE(-/-) mice on HFD. In a blinded test set, these polypeptides allowed identification of atherosclerosis at a sensitivity of 90% and specificity of 100%, as well as monitoring of disease progression. Sequencing of the discovered polypeptides identified fragments of α(1)-antitrypsin, epidermal growth factor (EGF), kidney androgen-regulated protein, and collagen. Using immunohistochemistry, α(1)-antitrypsin, EGF, and collagen type I were shown to be highly expressed in atherosclerotic plaques of ApoE(-/-) mice on HFD. Urinary excretion levels of collagen and α(1)-antitrypsin fragments also significantly correlated with intraplaque collagen and α(1)-antitrypsin content, mirroring plaque protein expression in the urine proteome. To provide further confirmation that the newly identified proteins are relevant in humans, the presence of collagen type I, α(1)-antitrypsin, and EGF was also confirmed in human atherosclerotic disease. Urine proteome analysis in mice exemplifies the potential of a novel multimarker approach for the noninvasive detection of atherosclerosis and monitoring of disease progression. Furthermore, this approach represents a novel discovery tool for the identification of proteins relevant in murine and human atherosclerosis and thus also defines potential novel therapeutic targets.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apolipoproteins E - deficiency
- Apolipoproteins E - genetics
- Atherosclerosis - diagnosis
- Atherosclerosis - etiology
- Atherosclerosis - genetics
- Atherosclerosis - urine
- Biomarkers - urine
- Collagen Type I - urine
- Diet, High-Fat - adverse effects
- Disease Progression -
- Electrophoresis, Capillary -
- Epidermal Growth Factor - urine
- Humans -
- Mass Spectrometry -
- Mice -
- Mice, Knockout -
- Peptides - urine
- Plaque, Atherosclerotic - diagnosis
- Plaque, Atherosclerotic - etiology
- Plaque, Atherosclerotic - genetics
- Plaque, Atherosclerotic - urine
- Proteome - metabolism
- Sensitivity and Specificity -
- Sequence Analysis, Protein -
- alpha 1-Antitrypsin - urine