Exaggerated neointima formation in human C-reactive protein transgenic mice is IgG Fc receptor type I (Fc gamma RI)-dependent.
Neointima formation after vascular injury is exaggerated in ovariectomized (OVX) human C-reactive protein transgenic mice (CRPtg) compared to nontransgenic mice (NTG). We tested the hypothesis that this CRP-mediated exacerbation requires IgG Fc receptors (Fc gamma Rs). OVX NTG, CRPtg, and CRPtg lacking Fc gamma RI, Fc gamma RIIb, Fc gamma RIII, or the common gamma chain (FcR gamma) had their common carotid artery ligated. Twenty-eight days later neointimal thickening in CRPtg/Fc gamma RI(-/-) and CRPtg/FcR gamma (-/-) was significantly less than in CRPtg and no worse than in NTG, whereas in CRPtg/Fc gamma RIIb(-/-) and CRPtg/Fc gamma RIII(-/-) neointimal thickness was equal to or greater than in CRPtg. Immunohistochemistry revealed human CRP in the neointima of CRPtg, but little or none was observed in those lacking Fc gamma RI or FcR gamma. Real-time reverse transcriptase-polymerase chain reaction demonstrated that Fc gamma R types I to III were expressed in the CRPtg arteries, with Fc gamma RI expression increasing by threefold after ligation injury. Levels of serum complement (C3), neointimal deposition of complement (C3d), and cellular composition (monocytes, macrophages, lymphocytes) in the neointima did not differ among the different CRPtg genotypes. However, by immunofluorescence a neointimal population of F4/80+CRP+ cells was revealed only in OVX CRPtg. The exaggerated response to vascular injury provoked by CRP in OVX CRPtg depends on Fc gamma RI and probably requires its expression by F4/80+ cells.
Vascular Biology and Hypertension Program, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
Dongqi
D
Xing
Fadi G
FG
Hage
Yiu-Fai
YF
Chen
Mark A
MA
McCrory
Wenguang
W
Feng
Gregory A
GA
Skibinski
Erum
E
Majid-Hassan
Suzanne
S
Oparil
Alexander J
AJ
Szalai
D000818:Animals; D002097:C-Reactive Protein / Q000235:genetics*; D002339:Carotid Arteries / Q000473:pathology; D020212:Carotid Artery Injuries / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D017452:Receptors, IgG / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017452:Receptors, IgG; D002097:C-Reactive Protein