Increase in GLUT1 in smooth muscle alters vascular contractility and increases inflammation in response to vascular injury

Neeta Adhikari, David L. Basi, Marjorie Carlson, Ami Mariash, Zhigang Hong, Ute Lehman, Sureni Mullegama, Edward K. Weir, Jennifer L. Hall

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Objective- The goal of this study was to test the contributing role of increasing glucose uptake in vascular smooth muscle cells (VSMCs) in vascular complications and disease. Methods and results- A murine genetic model was established in which glucose trasporter 1 (GLUT1), the non-insulin-dependent glucose transporter protein, was overexpressed in smooth muscle using the sm22α promoter. Overexpression of GLUT1 in smooth muscle led to significant increases in glucose uptake (n=3, P<0.0001) as measured using radiolabeled 2-deoxyglucose. Fasting blood glucose, insulin, and nonesterified fatty acids were unchanged. Contractility in aortic ring segments was decreased in sm22α-GLUT1 mice (n=10, P<0.04). In response to vascular injury, sm22α-GLUT1 mice exhibited a proinflammatory phenotype, including a significant increase in the percentage of neutrophils in the lesion (n=4, P<0.04) and an increase in monocyte chemoattractant protein-1 (MCP-1) immunofluorescence. Circulating haptoglobin and glutathione/total glutathione were significantly higher in the sm22α-GLUT1 mice postinjury compared with controls (n=4, P<0.05), suggesting increased flux through the pentose phosphate pathway. sm22α-GLUT1 mice exhibited significant medial hypertrophy following injury that was associated with a significant increase in the percentage of VSMCs in the media staining positive for nuclear phosphoSMAD2/3 (n=4, P<0.003). Conclusion- In summary, these findings suggest that increased glucose uptake in VSMCs impairs vascular contractility and accelerates a proinflammatory, neutrophil-rich lesion in response to injury, as well as medial hypertrophy, which is associated with enhanced transforming growth factor-β activity.

Original languageEnglish (US)
Pages (from-to)86-94
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume31
Issue number1
DOIs
StatePublished - Jan 2011

Keywords

  • Glut1
  • glucose
  • haptoglobin
  • hypertrophy
  • macrophage
  • neutrophil
  • phosphoSMAD2/3
  • vascular smooth muscle

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