Nestin downregulation in rat vascular smooth muscle cells represents an early marker of vascular disease in experimental type I diabetes

Cardiovasc Diabetol. 2014 Aug 21;13:119. doi: 10.1186/s12933-014-0119-6.


Background: Nestin was reported to directly contribute to cell proliferation and the intermediate filament protein was detected in vascular smooth muscle cells. In experimental type I diabetes, nestin downregulation in the heart was identified as an incipient pathophysiological event. The following study tested the hypothesis that dysregulation of nestin expression in vascular smooth muscle cells represented an early event of vascular disease in experimental type I diabetes.

Methods/results: In the carotid artery and aorta of adult male Sprague-Dawley rats, a subpopulation of vascular smooth muscle cells co-expressed nestin and was actively involved in the cell cycle as reflected by the co-staining of nuclear phosphohistone-3. The infection of aortic vascular smooth muscle cells with a lentivirus containing a shRNAmir directed against nestin significantly reduced protein expression and concomitantly attenuated basal DNA synthesis. Two weeks following injection of adult male Sprague-Dawley rats with streptozotocin, the endothelial response of aortic rings to acetylcholine, vascular morphology and the total density of vascular smooth muscle cells in the vasculature of type I diabetic rats were similar to normal rats. By contrast, nestin protein levels and the density of nestin(+)/phosphohistone-3(+)-vascular smooth muscle cells were significantly reduced in type I diabetic rats. The in vivo observations were recapitulated in vitro as exposure of vascular smooth muscle cells to 30 mM D-glucose inhibited DNA synthesis and concomitantly reduced nestin protein expression.

Conclusions: Hyperglycaemia-mediated nestin downregulation and the concomitant reduction of cycling vascular smooth muscle cells represent early markers of vascular disease in experimental type I diabetes.

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 1 / pathology
  • Down-Regulation / physiology
  • Male
  • Muscle, Smooth, Vascular / metabolism*
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Myocytes, Smooth Muscle / pathology
  • Nestin / metabolism*
  • Organ Culture Techniques
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Diseases / metabolism*
  • Vascular Diseases / pathology


  • Biomarkers
  • Nes protein, rat
  • Nestin