Comparative proteomic analysis of rat aorta in a subtotal nephrectomy model
Resource
PROTEOMICS, 10(13), 2429-2443
Journal
PROTEOMICS
Journal Volume
10
Journal Issue
13
Pages
2429-2443
Date Issued
2010
Date
2010
Author(s)
Lin, Yao-Ping
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. ? 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
Subjects
Animal proteomics; Aorta; Cardiovascular; Subtotal nephrectomy
SDGs
Other Subjects
creatinine; enalapril; epidermal growth factor; heat shock protein 27; milk fat globule epidermal growth factor 8; unclassified drug; urea; dipeptidyl carboxypeptidase inhibitor; enalapril; heat shock protein 27; Hspb1 protein, rat; membrane antigen; MFGE8 protein, rat; milk protein; animal experiment; animal model; animal tissue; aorta; arterial stiffness; article; body weight; cardiovascular system; chronic kidney disease; clinical article; comparative study; controlled study; creatinine blood level; cytoskeleton; diastolic blood pressure; down regulation; experimental model; glomerulus filtration rate; heart rate; heart weight; human; immunohistochemistry; kidney function; male; nephrectomy; nonhuman; phenotype; priority journal; protein analysis; protein blood level; protein metabolism; protein processing; protein secretion; proteomics; pulse pressure; pulse wave; rat; systolic blood pressure; upregulation; urea blood level; Western blotting; animal; aorta; chemistry; disease model; drug effects; kidney disease; nephrectomy; pathology; pathophysiology; Sprague Dawley rat; Animalia; Rattus; Angiotensin-Converting Enzyme Inhibitors; Animals; Antigens, Surface; Aorta; Disease Models, Animal; Enalapril; HSP27 Heat-Shock Proteins; Humans; Kidney Diseases; Male; Milk Proteins; Nephrectomy; Proteomics; Rats; Rats, Sprague-Dawley
Type
journal article
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