title: Nitric oxide affects UbcH10 levels differently in type 1 and type 2 diabetic rats.
abstract: BACKGROUND
  Nitric oxide (NO) more effectively inhibits neointimal hyperplasia in type 2 diabetic versus nondiabetic and type 1 diabetic rodents. NO also decreases the ubiquitin-conjugating enzyme UbcH10, which is critical to cell-cycle regulation. This study seeks to determine whether UbcH10 levels in the vasculature of diabetic animal models account for the differential efficacy of NO at inhibiting neointimal hyperplasia.
  
  
  METHODS
  Vascular smooth muscle cells (VSMCs) harvested from nondiabetic lean Zucker (LZ) and type 2 diabetic Zucker diabetic fatty (ZDF) rats were exposed to high glucose (25 mM) and high insulin (24 nM) conditions to mimic the diabetic environment in vitro. LZ, streptozotocin-injected LZ (STZ, type 1 diabetic), and ZDF rats underwent carotid artery balloon injury (±10 mg PROLI/NO), and vessels were harvested at 3 and 14 d. UbcH10 was assessed by Western blotting and immunofluorescent staining.
  
  
  RESULTS
  NO more effectively reduced UbcH10 levels in LZ versus ZDF VSMCs; however, addition of insulin and glucose dramatically potentiated the inhibitory effect of NO on UbcH10 in ZDF VSMCs. Three days after balloon injury, Western blotting showed NO decreased free UbcH10 and increased polyubiquitinated UbcH10 levels by 35% in both STZ and ZDF animals. Fourteen days after injury, immunofluorescent staining showed increased UbcH10 levels throughout the arterial wall in all animal models. NO decreased UbcH10 levels in LZ and STZ rats but not in ZDF.
  
  
  CONCLUSIONS
  These data suggest a disconnect between UbcH10 levels and neointimal hyperplasia formation in type 2 diabetic models and contribute valuable insight regarding differential efficacy of NO in these models.
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Monica P
authors: MP
authors: Rodriguez
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Nick D
authors: ND
authors: Tsihlis
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Zachary M
authors: ZM
authors: Emond
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Zheng
authors: Z
authors: Wang
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Vinit N
authors: VN
authors: Varu
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Qun
authors: Q
authors: Jiang
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
authors: Janet M
authors: JM
authors: Vercammen
authors: Division of Vascular Surgery, Department of Surgery, and Simpson Querrey Institute for BioNanotechnology, Northwestern University Feinberg School of Medicine, Chicago, Illinois; Division of Vascular Surgery, Department of Surgery, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois. Electronic address: mkibbe@nmh.org.
authors: Melina R
authors: MR
authors: Kibbe
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000473:pathology; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry; D058426:Neointima / Q000473:pathology; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D013311:Streptozocin; D044763:Ubiquitin-Conjugating Enzymes / Q000097:blood*; D054875:Ubiquitination
chemical_list: D001786:Blood Glucose; D009569:Nitric Oxide; D013311:Streptozocin; C546779:Ube2c protein, mouse; D044763:Ubiquitin-Conjugating Enzymes
keywords: Artery; Diabetes; Neointimal hyperplasia; UbcH10; Ubiquitin