Prevention of diabetes-induced arginase activation and vascular dysfunction by Rho kinase (ROCK) knockout

Lin Yao, Surabhi Chandra, Haroldo A. Toque, Anil Bhatta, Modesto Rojas, Ruth B. Caldwell, R. William Caldwell

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

AimsWe determined the role of the Rho kinase (ROCK) isoforms in diabetes-induced vascular endothelial dysfunction and enhancement of arginase activity and expression.Methods and resultsStudies were performed in aortic tissues from haplo-insufficient (H-I) ROCK1 and ROCK2 mice and wild-type (WT) mice rendered diabetic with streptozotocin and in bovine aortic endothelial cells (BAECs) treated with high glucose (HG, 25 mM). Protein expression of both ROCK isoforms was substantially elevated in aortas of WT mice after 8 weeks of diabetes and in BAECs after 48 h in HG. Impairment of endothelium-dependent vasorelaxation of aortas was observed in diabetic WT mice. However, there was no impairment in aortas of diabetic ROCK1 H-I mice and less impairment in aortas of diabetic ROCK2 H-I mice, compared with non-diabetic mice. These vascular effects were associated with the prevention of diabetes-induced decrease in nitric oxide (NO) production and a rise in arginase activity/expression. Acute treatment with the arginase inhibitor, BEC, improved endothelium-dependent vasorelaxation of aortas of both diabetic WT and ROCK2, but not of ROCK1 mice.ConclusionPartial deletion of either ROCK isoform, but to a greater extent ROCK1, attenuates diabetes-induced vascular endothelial dysfunction by preventing increased arginase activity and expression and reduction in NO production in type 1 diabetes. Limiting ROCK and arginase activity improves vascular function in diabetes.

Original languageEnglish (US)
Pages (from-to)509-519
Number of pages11
JournalCardiovascular research
Volume97
Issue number3
DOIs
StatePublished - Mar 1 2013

Keywords

  • Arginase
  • Isoforms
  • Rho kinase
  • Type 1 diabetes
  • Vascular function

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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