TY - JOUR
T1 - Evaluation of the Zucker Diabetic Fatty (ZDF) Rat as a Model for Human Disease Based on Urinary Peptidomic Profiles
AU - Siwy, Justyna
AU - Zoja, Carlamaria
AU - Klein, Julie
AU - Benigni, Ariela
AU - Mullen, Wiliam
AU - Mayer, Bernd
AU - Mischak, Harald
AU - Jankowski, Joachim
AU - Stevens, Robert
AU - Vlahou, Antonia
AU - Kossida, Sophia
AU - Perco, Paul
AU - Bahlmann, Ferdinand H.
PY - 2012/12/7
Y1 - 2012/12/7
N2 - 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. © 2012 Siwy et al.
AB - 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. © 2012 Siwy et al.
U2 - 10.1371/journal.pone.0051334
DO - 10.1371/journal.pone.0051334
M3 - Article
VL - 7
JO - PLoS ONE
JF - PLoS ONE
IS - 12
M1 - e51334
ER -
