Increased neointima formation in cysteine-rich protein 2-deficient mice in response to vascular injury.
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 alpha-actin, SM22alpha, 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.
Wei
Jiao
J
Pulmonary and Critical Care Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Gorman
Terri E
TE
Liu
Xiaoli
X
Ith
Bonna
B
Tseng
Alan
A
Chen
Zhiping
Z
Simon
Daniel I
DI
Layne
Matthew D
MD
Yet
Shaw-Fang
SF
D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D049109:Cell Proliferation; D004730:Endothelium, Vascular / Q000502:physiology; D060588:LIM Domain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D017539:Tunica Intima / Q000473:pathology*
C484376:Csrp2 protein, mouse; D060588:LIM Domain Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger