title: Evaluation of the Zucker diabetic fatty (ZDF) rat as a model for human disease based on urinary peptidomic profiles.
abstract: Representative animal models for diabetes-associated vascular complications are extremely relevant in assessing potential therapeutic drugs. While several rodent models for type 2 diabetes (T2D) are available, their relevance in recapitulating renal and cardiovascular features of diabetes in man is not entirely clear. Here we evaluate at the molecular level the similarity between Zucker diabetic fatty (ZDF) rats, as a model of T2D-associated vascular complications, and human disease by urinary proteome analysis. Urine analysis of ZDF rats at early and late stages of disease compared to age- matched LEAN rats identified 180 peptides as potentially associated with diabetes complications. Overlaps with human chronic kidney disease (CKD) and cardiovascular disease (CVD) biomarkers were observed, corresponding to proteins marking kidney damage (eg albumin, alpha-1 antitrypsin) or related to disease development (collagen). Concordance in regulation of these peptides in rats versus humans was more pronounced in the CVD compared to the CKD panels. In addition, disease-associated predicted protease activities in ZDF rats showed higher similarities to the predicted activities in human CVD. Based on urinary peptidomic analysis, the ZDF rat model displays similarity to human CVD but might not be the most appropriate model to display human CKD on a molecular level.
authors.affiliation: Mosaiques Diagnostics, Hannover, Germany.
authors.forename: Justyna
authors.initials: J
authors.lastname: Siwy
authors.forename: Carlamaria
authors.initials: C
authors.lastname: Zoja
authors.forename: Julie
authors.initials: J
authors.lastname: Klein
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.forename: Wiliam
authors.initials: W
authors.lastname: Mullen
authors.forename: Bernd
authors.initials: B
authors.lastname: Mayer
authors.forename: Harald
authors.initials: H
authors.lastname: Mischak
authors.forename: Joachim
authors.initials: J
authors.lastname: Jankowski
authors.forename: Robert
authors.initials: R
authors.lastname: Stevens
authors.forename: Antonia
authors.initials: A
authors.lastname: Vlahou
authors.forename: Sophia
authors.initials: S
authors.lastname: Kossida
authors.forename: Paul
authors.initials: P
authors.lastname: Perco
authors.forename: Ferdinand H
authors.initials: FH
authors.lastname: Bahlmann
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine*; D016000:Cluster Analysis; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000473:pathology*; D004195:Disease Models, Animal; D019075:Electrophoresis, Capillary; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D009206:Myocardium / Q000378:metabolism; D010455:Peptides / Q000652:urine*; D040901:Proteomics; D051381:Rats; D011924:Rats, Zucker / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D010455:Peptides