SPARC gene expression is increased in diabetes-related mesenteric vascular hypertrophy

K. Jandeleit-Dahm, J. Rumble, A. J. Cox, D. J. Kelly, M. Dziadek, M. E. Cooper, R. E. Gilbert

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Abstract

The anti-adhesive extracellular matrix protein SPARC (secreted protein and rich in cysteine; osteonectin or BM40) has been implicated in the regulation of matrix turnover, cell migration, and proliferation. The present study sought to examine whether modulation in the expression of this protein may play a role in diabetes-associated vascular remodeling. SPARC mRNA and protein were measured in mesenteric vessels of diabetic rats and controls. Hypertrophy of mesenteric vessels was noted after 3 and 32 weeks of diabetes as revealed by the increase in mesenteric vessel wet weight and an increased wall/lumen ratio. SPARC mRNA was sparsely present in intima and adventitia of control vessels. There was a marked increase in SPARC gene expression in the intima and adventitia of mesenteric vessels after 1, 3, and 32 weeks of diabetes. SPARC protein was demonstrated in the vessel wall in control animals and was increased in the mesenteric vessels of diabetic rats after 1 and 32 weeks of diabetes. Administration of the inhibitor of advanced glycation end-product formation, aminoguanidine, to diabetic rats attenuated both the hypertrophic response in mesenteric vessels and the overexpression of SPARC mRNA and protein without affecting glycemic control or food intake. In summary, diabetes-related mesenteric vascular hypertrophy is associated with an increase in SPARC expression in the vessel wall. The modulation of SPARC expression in mesenteric vessels of diabetic rats might be of pathogenetic significance in the development of vascular remodeling in diabetes. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)61-71
Number of pages11
JournalMicrovascular Research
Volume59
Issue number1
DOIs
Publication statusPublished - 1 Jan 2000
Externally publishedYes

Keywords

  • Diabetes mellitus
  • Mesenteric vessels
  • mRNA
  • Osteonectin
  • Remodeling
  • SPARC
  • Vascular hypertrophy

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