title: Phenotypic modulation of mesenteric vascular smooth muscle cells from type 2 diabetic rats is associated with decreased caveolin-1 expression.
abstract: OBJECTIVE
  Diabetes-induced vascular complications are associated with vascular smooth muscle cell (VSMC) phenotypic modulation, switching from a contractile to a synthetic-proliferative phenotype. Loss of caveolin-1 is involved with proliferation of VSMCs. We tested the hypothesis that mesenteric VSMCs from type 2 diabetic Goto-Kakizaki (GK) rat undergo phenotypic modulation and it is linked to decreased caveolin-1 expression.
  
  
  METHODS
  VSMCs were isolated from mesenteric arteries from GK rats and age-matched control Wistar rats. Western blotting was used to determine expression of target proteins such as caveolin-1, calponin (marker of differentiation), and proliferating cell nuclear antigen (PCNA, marker of proliferation). In addition, we measured intracellular reactive oxygen species (ROS) production using H2DCF-DA and activation of extracellular signal-regulated kinase (ERK1/2) by western blotting in VSMCs from GK stimulated with lipopolysaccharide (LPS), an endotoxin upregulated in diabetes.
  
  
  RESULTS
  Mesenteric VSMCs from diabetic GK rats exhibited decreased caveolin-1 and calponin expression and increased PCNA expression compared to control. Increased levels of ROS and phospho-ERK1/2 expression were also found in GK VSMCs. LPS augmented ROS and phosphorylated ERK1/2 levels to a greater extent in GK VSMCs than in control. Likewise, high glucose decreased caveolin-1 and calponin expression, increased PCNA expression and augmented ROS production in control mesenteric VSMCs.
  
  
  CONCLUSIONS
  These results suggest that mesenteric VSMCs from diabetic GK rats undergo phenotypic modulation and it is associated with decreased caveolin-1 expression. These alterations may be due to enhanced inflammatory stimuli and glucose levels present in diabetic milieu.
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA, USA.
authors.forename: Maria Alicia
authors.initials: MA
authors.lastname: Carrillo-Sepulveda
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D051242:Caveolin 1 / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008297:Male; D008638:Mesenteric Arteries / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology; D000096985:Calponins
chemical_list: D002135:Calcium-Binding Proteins; D051242:Caveolin 1; D048049:Extracellular Signal-Regulated MAP Kinases; D008840:Microfilament Proteins; D017382:Reactive Oxygen Species; D000096985:Calponins