Arginase promotes neointima formation in rat injured carotid arteries

Kelly J. Peyton, Diana Ensenat, Mohammed A. Azam, Amit N. Keswani, Sankaranarayanan Kannan, Xiao Ming Liu, Hong Wang, David A. Tulis, William Durante

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

OBJECTIVE: Arginase stimulates the proliferation of cultured vascular smooth muscle cells (VSMCs); however, the influence of arginase on VSMC growth in vivo is not known. This study investigated the impact of arginase on cell cycle progression and neointima formation after experimental arterial injury. METHODS AND RESULTS: Balloon injury of rat carotid arteries resulted in a sustained increase in arginase activity in the vessel wall and the induction of arginase I protein in both the media and neointima of injured vessels. Furthermore, local perivascular application of the potent and selective arginase inhibitors S-(2-boronoethyl)-l-cysteine (BEC) or N-hydroxy-nor-l-arginine (L-OHNA) immediately after injury markedly attenuated medial and neointimal DNA synthesis and neointima formation. Substantial arginase I protein and arginase activity was also detected in rat cultured aortic VSMCs. Moreover, treatment of VSMCs with BEC or L-OHNA, or knockdown of arginase I protein, arrested cells in the G0/G1 phase of the cell cycle and induced the expression of the cyclin-dependent protein kinase inhibitor, p21. CONCLUSION: This study demonstrates that arginase is essential for VSMCs to enter the cell cycle and that arginase I contributes to the remodeling response after arterial injury. Arginase I represents a potentially new therapeutic target for the treatment of vasculoproliferative disorders.

Original languageEnglish
Pages (from-to)488-494
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2009
Externally publishedYes

Keywords

  • Arginase
  • Neointima
  • Vascular smooth muscle cell proliferation

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