Neointimal formation is reduced after arterial injury in human crp transgenic mice

Haim D. Danenberg, Etty Grad, Rajesh V. Swaminathan, Zhiping Chen, Philip Seifert, Alexander J. Szalai, Chaim Lotan, Daniel I. Simon, Elazer R. Edelman

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Objectives/Methods: Elevated CRP levels predict increased incidence of cardiovascular events and poor outcomes following interventions. There is the suggestion that CRP is also a mediator of vascular injury. Transgenic mice carrying the human CRP gene (CRPtg) are predisposed to arterial thrombosis post-injury. We examined whether CRP similarly modulates the proliferative and hyperplastic phases of vascular repair in CRPtg when thrombosis is controlled with daily aspirin and heparin at the time of trans-femoral arterial wire-injury. Results: Complete thrombotic arterial occlusion at 28 days was comparable for wild-type and CRPtg mice (14 and 19%, respectively). Neointimal area at 28d was 2.5 fold lower in CRPtg (4190 ± 3134 μm2, n = 12) compared to wild-types (10,157 ± 8890 μm2, n = 11, p < 0.05). Likewise, neointimal/media area ratio was 1.10 ± 0.87 in wild-types and 0.45 ± 0.24 in CRPtg (p < 0.05). Seven days post-injury, cellular proliferation and apoptotic cell number in the intima were both less pronounced in CRPtg than wild-type. No differences were seen in leukocyte infiltration or endothelial coverage. CRPtg mice had significantly reduced p38 MAPK signaling pathway activation following injury. Conclusions: The pro-thrombotic phenotype of CRPtg mice was suppressed by aspirin/heparin, revealing CRP's influence on neointimal growth after trans-femoral arterial wire-injury. Signaling pathway activation, cellular proliferation, and neointimal formation were all reduced in CRPtg following vascular injury. Increasingly we are aware of CRP multipotent effects. Once considered only a risk factor, and recently a harmful agent, CRP is a far more complex regulator of vascular biology.

Original languageEnglish
Pages (from-to)85-91
Number of pages7
JournalAtherosclerosis
Volume201
Issue number1
DOIs
StatePublished - Nov 2008
Externally publishedYes

Keywords

  • Angioplasty
  • C-reactive protein
  • Neointima
  • p38 MAPK

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