title: Neointimal formation is reduced after arterial injury in human crp transgenic mice.
abstract: OBJECTIVE
  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.
authors: Department of Cardiology, Hadassah-Hebrew University Medical Center, 91120 Jerusalem, Israel; Harvard-MIT, Division of Health Sciences and Technology, Cambridge, MA, UK. danen@md.huji.ac.il
authors: Haim D
authors: HD
authors: Danenberg
authors: Etty
authors: E
authors: Grad
authors: Rajesh V
authors: RV
authors: Swaminathan
authors: Zhiping
authors: Z
authors: Chen
authors: Philip
authors: P
authors: Seifert
authors: Alexander J
authors: AJ
authors: Szalai
authors: Chaim
authors: C
authors: Lotan
authors: Daniel I
authors: DI
authors: Simon
authors: Elazer R
authors: ER
authors: Edelman
mesh_terms: D017130:Angioplasty / Q000009:adverse effects; D000818:Animals; D017209:Apoptosis; D002097:C-Reactive Protein / Q000502:physiology*; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000293:injuries* / Q000473:pathology*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013927:Thrombosis / Q000209:etiology* / Q000473:pathology / Q000517:prevention & control; D017539:Tunica Intima / Q000473:pathology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D005343:Fibrinolytic Agents; D002097:C-Reactive Protein; D048051:p38 Mitogen-Activated Protein Kinases