Abstract 657: Fcγ Receptors Enable Human C-Reactive Protein to Exacerbate Neointima Formation in Transgenic Mice
Background: We showed that locally expressed human C-reactive protein (CRP) enhances neointimal formation following acute (ligation-induced) vascular injury in human CRP transgenic(CRPtg) mice. Activated granulocytes, macrophages and vascular smooth muscle cells (VSMCs) are major constitunents of ligation induced arterial lesions, and can influence the repair processes via several potential mechanism. Both activating IgG Fc receptors (FcγRs), FcγRI and FcγRIII, and the inhibitory receptor FcγRIIb, are expressed by leukocytes and VSMCs, and CRP bind each of these with varying affinities. Experiments was performed to determine if FcγR was required for CRP-mediated exacebation of vascular injury in the CRPtg mouse and if so, which FcγR type was involved.
Methods and Results: Neointima formation was measured in ovariectomized (OVX) CRPtg and in CRPtg lacking individual FcγRs or lacking the FcR common γ-chain, which is required for functional expression of FcγRI and FcγRIII. 28 days after right common carotid artery ligation, morphometric analysis revealed that FcRγ chain-deficient CRPtg had less nointima formation than CRPtg, whereas CRPtg lacking expression of Fcγ RIIb or FcγRIII had more pronounced neointima formation (Figure⇓).
Conclusion: CRP-mediated exacerbation of the vascular injury response in CRPtg mice requires the FcR common γ-chain but not the FcγR type IIb and III. We predict that FcγRI is the FcγR that promotes the deleterious action of CRP in the vessel wall. Experiments with CRPtg/FcγRI-deficient mice are ongoing. Area of neointima, media, and neointima/media ratio in mice after carotid artery ligation. Mean±SEM, (n)= Number of mice, *P<0.05 vs CRPtg.