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

Academic Article


  • 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. © 2008 Elsevier Ireland Ltd. All rights reserved.
  • Published In

  • Atherosclerosis  Journal
  • Digital Object Identifier (doi)

    Author List

  • Danenberg HD; Grad E; Swaminathan RV; Chen Z; Seifert P; Szalai AJ; Lotan C; Simon DI; Edelman ER
  • Start Page

  • 85
  • End Page

  • 91
  • Volume

  • 201
  • Issue

  • 1