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

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 μm 2 , n = 12) compared to wild-types (10,157 ± 8890 μm 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.

Effects of Human C-Reactive Protein on Pathogenesis of Features of the Metabolic Syndrome

“…Given the potential benefits of transgenic approaches for investigating the biologic effects of increased levels of CRP, many investigators have used transgenic mice expressing human CRP to study its role in atherosclerosis and cardiovascular function14–19. However, relatively little work has been done in these models with respect to pathogenesis of features of the metabolic syndrome and risk factors for diabetes.…”

Fcγ Receptors and Ligands and Cardiovascular Disease

“…94 Furthermore, there is evidence that the impact of FcγR and their ligands on neointima development may relate to their modulation of thrombosis, since in a trans-femoral artery wire injury model in which thrombosis was controlled with aspirin and heparin, CRP transgenic mice displayed less neointima formation. 95 The interpretation of findings regarding neointima development with FcγR manipulation may be complex because the FcγR γ chain plays a key role in platelet activation by collagen, and platelet activation may be instrumental to neointima initiation and progression. 96 Overall, the animal model data available to date indicate that FcγR impact thrombotic and non-thrombotic vascular occlusion.…”

Serum C-reactive Protein As a Possible Marker to Predict Delayed Hemorrhage After Colonoscopic Polypectomy

“…Thus, those with chronic ischemia with elevated levels of CRP may have compromised eNO production and attenuated proliferation of EPC that may impedes healing process [22]. This is supported by the observation that mice with elevated levels of CRP showed a significantly faster and higher rate of arterial thrombosis [23]. Furthermore, volunteers receiving recombinant human CRP (rh-CRP) showed inappropriately activated coagulation system [24].…”