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(Circulation Research. 2005;97:1323.)
© 2005 American Heart Association, Inc.

Integrative Physiology

Increased Neointima Formation in Cysteine-Rich Protein 2–Deficient Mice in Response to Vascular Injury

Jiao Wei, Terri E. Gorman, Xiaoli Liu, Bonna Ith, Alan Tseng, Zhiping Chen, Daniel I. Simon, Matthew D. Layne, Shaw-Fang Yet

From the Pulmonary and Critical Care (J.W., X.L., B.I., A.T., M.D.L., S.-F.Y.) and Cardiovascular (Z.C., D.I.S.) Divisions, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; and the Division of Newborn Medicine (T.E.G.), Children’s Hospital, Boston, Mass.

Correspondence to Shaw-Fang Yet, Brigham and Women’s Hospital, 75 Francis St, Thorn 932A, Boston, MA 02115. E-mail syet{at}rics.bwh.harvard.edu

In response to arterial injury, medial vascular smooth muscle cells (VSMCs) proliferate and migrate into the intima, contributing to the development of occlusive vascular disease. The LIM protein cysteine-rich protein (CRP) 2 associates with the actin cytoskeleton and may maintain the cytoarchitecture. CRP2 also interacts with transcription factors in the nucleus to mediate SMC gene expression. To test the hypothesis that CRP2 may be an important regulator of vascular development or function we generated Csrp2 (gene symbol of the mouse CRP2 gene)-deficient (Csrp2^–/–) mice by targeted mutation. Csrp2^–/– mice did not have any gross vascular defects or altered expression levels of SM -actin, SM22, or calponin. Following femoral artery injury, CRP2 expression persisted in the vessel wall at 4 days and then decreased by 14 days. Intimal thickening was enhanced 3.4-fold in Csrp2^–/– compared with wild-type (WT) mice 14 days following injury. Cellular proliferation was similar between WT and Csrp2^–/– VSMC both in vivo and in vitro. Interestingly, Csrp2^–/– VSMC migrated more rapidly in response to PDGF-BB and had increased Rac1 activation. Our data demonstrate that CRP2 is not required for vascular development. However, an absence of CRP2 enhanced VSMC migration and increased neointima formation following arterial injury.

Key Words: arterial wire injury • vascular smooth muscle cells • migration

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