Comparative proteomic analysis of rat aorta in a subtotal nephrectomy model

Yao Ping Lin, Meng Erh Hsu, Yi Ying Chiou, Hung Yi Hsu, Hiao Chien Tsai, Yu Ju Peng, Chi Yu Lu, Chien Yuan Pan, Wen Chung Yu, Chen Huan Chen, Chin Wen Chi, Chao Hsiung Lin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Although accelerated atherosclerosis and arteriosclerosis are the main causes of cardiovascular morbidity and mortality in chronic kidney disease (CKD) patients, the molecular pathogenesis remains largely obscure. Our study of the aortic function in a typical CKD model of subtotal nephrectomy (SNX) rats demonstrated phenotypes that resemble CKD patients with aortic stiffness. The 2-DE analysis of rat aortas followed by MS identified 29 up-regulated and 53 downregulated proteins in SNX rats. Further Western blot and immunohistochemistry analyses validated the decreased HSP27 and increased milk fat globule epidermal growth factor-8 (MFGE8) in SNX rats. Functional classification of differential protein profiles using KOGnitor revealed that the two major categories involved in aortic stiffness are posttranslational modifi-cation, protein turnover, chaperones (23%) and cytoskeleton (21%). Ingenuity Pathway Analysis highlighted cellular assembly and organization, and cardiovascular system development and function as the two most relevant pathways. Among the identified proteins, the clinical significance of the secreted protein MFG-E8 was confirmed in 50 CKD patients, showing that increased serum MFG-E8 level is positively related to aortic stiffness and renal function impairment. Drug interventions with an inhibitor of the angiotensin converting enzyme, enalapril, in SNX rats improved aortic stiffness and decreased MFG-E8 depositions. Together, our studies provide a repertoire of potential biomarkers related to the aortic stiffness in CKD.

Original languageEnglish
Pages (from-to)2429-2443
Number of pages15
JournalProteomics
Volume10
Issue number13
DOIs
StatePublished - Jul 2010

Keywords

  • Animal proteomics
  • Aorta
  • Cardiovascular
  • Subtotal nephrectomy

Fingerprint

Dive into the research topics of 'Comparative proteomic analysis of rat aorta in a subtotal nephrectomy model'. Together they form a unique fingerprint.

Cite this