Comparative proteomic analysis of rat aorta in a subtotal nephrectomy model.
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 down-regulated proteins in SNX rats. Further Western blot and immunohistochemistry analyses validated the decreased HSP27 and increased milk fat globule epidermal growth factor-8 (MFG-E8) in SNX rats. Functional classification of differential protein profiles using KOGnitor revealed that the two major categories involved in aortic stiffness are posttranslational modification, 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.
Lin
Yao-Ping
YP
Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.
Hsu
Meng-Erh
ME
Chiou
Yi-Ying
YY
Hsu
Hung-Yi
HY
Tsai
Hiao-Chien
HC
Peng
Yu-Ju
YJ
Lu
Chi-Yu
CY
Pan
Chien-Yuan
CY
Yu
Wen-Chung
WC
Chen
Chen-Huan
CH
Chi
Chin-Wen
CW
Lin
Chao-Hsiung
CH
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000954:Antigens, Surface; D001011:Aorta / Q000737:chemistry* / Q000187:drug effects; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008894:Milk Proteins / Q000032:analysis; D009392:Nephrectomy; D040901:Proteomics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000806:Angiotensin-Converting Enzyme Inhibitors; D000954:Antigens, Surface; D055551:HSP27 Heat-Shock Proteins; C486114:Hspb1 protein, rat; C499941:MFGE8 protein, rat; D008894:Milk Proteins; D004656:Enalapril