title: Proteomic analysis reveals downregulation of housekeeping proteins in the diabetic vascular proteome.
abstract: OBJECTIVE
  Type 2 diabetes (T2D) increases the risk of death associated with cardiovascular complications. However, a complete understanding of protein changes within the diabetic vasculature is still lacking.
  
  
  METHODS
  Herein, we utilized mass spectrometry to perform vascular and urinary proteome analysis using a rat model of high-fat feeding and low-dose streptozotocin to simulate late-stage T2D. The purpose of this study was to identify aortic and urine proteins that are differentially expressed in normal and T2D rats.
  
  
  RESULTS
  High-fat feeding and low-dose streptozotocin resulted in hyperglycemia, hypoinsulinemia and high levels of circulating free fatty acids. Using a shotgun proteomic approach, high-mobility-group protein B1 and spondin-1 were significantly increased in T2D aorta compared to control aorta, suggesting vascular inflammation and smooth muscle proliferation, respectively. However, the majority of differentially expressed aortic proteins were downregulated in T2D, including proteins associated with coagulation, cell differentiation and redox homeostasis. Strikingly, we report a significant downregulation of commonly used cytoskeletal housekeeping proteins in T2D aorta. Urine from T2D rats displayed increased expression of proteins involved in inflammation and oxidative stress and decreased expression of proteins associated with lipid metabolism and cell adhesion. A number of differentially expressed proteins in urine of T2D rats have previously been reported in human T2D, thereby supporting this animal model as a good representation of human T2D.
  
  
  CONCLUSIONS
  Our data offer new information regarding key pathways that could be therapeutically targeted to combat the cardiovascular complications of T2D.
authors: Discipline of Human Physiology, School of Medicine, Flinders University, Room 4E 432, Flinders Medical Centre, Flinders Drive, Bedford Park, SA, 5042, Australia.
authors: Josua
authors: J
authors: Dwinovan
authors: Discipline of Human Physiology, School of Medicine, Flinders University, Room 4E 432, Flinders Medical Centre, Flinders Drive, Bedford Park, SA, 5042, Australia.
authors: Alexander D
authors: AD
authors: Colella
authors: Discipline of Human Physiology, School of Medicine, Flinders University, Room 4E 432, Flinders Medical Centre, Flinders Drive, Bedford Park, SA, 5042, Australia.
authors: Nusha
authors: N
authors: Chegeni
authors: Discipline of Human Physiology, School of Medicine, Flinders University, Room 4E 432, Flinders Medical Centre, Flinders Drive, Bedford Park, SA, 5042, Australia.
authors: Timothy K
authors: TK
authors: Chataway
authors: Discipline of Human Physiology, School of Medicine, Flinders University, Room 4E 432, Flinders Medical Centre, Flinders Drive, Bedford Park, SA, 5042, Australia. elke.sokoya@flinders.edu.au.
authors: Elke M
authors: EM
authors: Sokoya
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood / Q000378:metabolism / Q000652:urine; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000378:metabolism* / Q000652:urine; D015536:Down-Regulation; D020043:Genes, Essential; D050356:Lipid Metabolism; D008297:Male; D018384:Oxidative Stress; D020543:Proteome / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015415:Biomarkers; D020543:Proteome
keywords: Aorta; Diabetes; Proteomics; Urine; Vasculature