Neointimal formation is reduced after arterial injury in human crp transgenic mice.
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.
Danenberg
Haim D
HD
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
Grad
Etty
E
Swaminathan
Rajesh V
RV
Chen
Zhiping
Z
Seifert
Philip
P
Szalai
Alexander J
AJ
Lotan
Chaim
C
Simon
Daniel I
DI
Edelman
Elazer R
ER
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
D005343:Fibrinolytic Agents; D002097:C-Reactive Protein; D048051:p38 Mitogen-Activated Protein Kinases