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

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 microm(2), n=12) compared to wild-types (10,157+/-8890 microm(2), 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.