CX3CR1 deficiency confers protection from intimal hyperplasia after arterial injury.
OBJECTIVE
A functional polymorphism in the chemokine receptor CX3CR1 is associated with protection from vascular diseases including coronary artery disease and internal carotid artery occlusive disease. We investigated the mechanisms by which CX3CR1 may be involved by evaluating the inflammatory response to arterial injury in CX3CR1-deficient animals.


RESULTS
Femoral arteries of CX3CR1-/- and wild-type (WT) mice were injured with an angioplasty guide wire. After 1, 5, 14, and 28 days, arteries were harvested and evaluated by histology, morphometry, and immunohistochemistry. Arterial injury upregulated the CX3CR1 ligand CX3CL1. In CX3CR1-/- compared with WT animals, the incidence of neointima formation was 58% lower (P=0.0017), accompanied by no difference in the area of platelet accumulation at day 1 (P=0.48) but a significant decrease in intimal monocyte infiltration at day 5 (P=0.006), vascular smooth muscle cell (VSMC) proliferation at days 5 and 14, and intimal area at day 28 (P=0.009).


CONCLUSIONS
In an endothelial denudation injury model, CX3CR1 deficiency protects animals from developing intimal hyperplasia as a result of decreased monocyte trafficking to the lesion. CX3CR1 deficiency decreases VSMC proliferation and intimal accumulation either directly or indirectly as a result of defective monocyte infiltration.
Liu
Peng
P
Department of Medicine, University of North Carolina at Chapel Hill, USA.
Patil
Sarita
S
Rojas
Mauricio
M
Fong
Alan M
AM
Smyth
Susan S
SS
Patel
Dhavalkumar D
DD
D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002455:Cell Division; D002465:Cell Movement; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism* / Q000473:pathology; D006965:Hyperplasia; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes; D009131:Muscle, Smooth, Vascular / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle; D010979:Platelet Function Tests; D019707:Receptors, Chemokine / Q000172:deficiency*; D017539:Tunica Intima / Q000473:pathology*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology
D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine