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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2056.)
© 2006 American Heart Association, Inc.

Vascular Biology

CX₃CR1 Deficiency Confers Protection From Intimal Hyperplasia After Arterial Injury

Peng Liu; Sarita Patil; Mauricio Rojas; Alan M. Fong; Susan S. Smyth; Dhavalkumar D. Patel

From the Department of Medicine (P.L., M.R., A.M.F., S.S.S., D.D.P.), Thurston Arthritis Research Center (P.L., S.P., A.M.F., D.D.P.), and Carolina Cardiovascular Biology Center (M.R., S.S.S.), University of North Carolina at Chapel Hill, Chapel Hill, NC.

Correspondence to Dhavalkumar D. Patel, Novartis Institutes for BioMedical Research, WSJ 386.11.25, CH-4002 Basel, Switzerland. E-mail dhavalkumar.patel{at}novartis.com

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.

Methods and 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.

The chemokine receptor CX₃CR1 has been implicated in the pathogenesis of vascular diseases. In a guidewire-induced femoral artery injury model, the CX₃CR1 ligand (CX₃CL1) was induced by arterial injury. CX₃CR1 deficiency protected mice from developing intimal hyperplasia as a result of decreased monocyte trafficking to the lesion and VSMC proliferation.

Key Words: CX3CR1 • monocytes • smooth muscle cells • intimal hyperplasia • vascular biology

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