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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2002;22:528.)
© 2002 American Heart Association, Inc.

Editorials

Pleiotropic Effects of Chemokines in Vascular Lesion Development

Robert E. Gerszten

From the Massachusetts General Hospital, Center for Immunology and Inflammatory Diseases, Charlestown, Mass.

Correspondence to Robert Gerszten, Massachusetts General Hospital, Center for Immunology and Inflammatory Diseases, Charlestown, MA 02129. E-mail gerszten@cvrc.mgh.harvard

In the current issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Roque et al¹ studied the response to arterial injury in animals deficient in the monocyte chemoattractant protein-1 (MCP-1) receptor, CCR2. One month after the insult, CCR2 knockout mice showed a profound reduction in intimal area compared with their wild-type littermates. Surprisingly, there was no significant difference in leukocyte accumulation in the arterial wall between the two groups. The authors acknowledge that vascular wounding in mice does not necessarily recapitulate the biology of human atherogenesis or even percutaneous interventions. Nonetheless, the results of their studies are extremely provocative. These unanticipated findings contrast with our preconceived notions of direct links between chemokines, leukocyte accumulation, and vascular lesions.

See page 554

The prevailing dogma suggests that aberrant chemokine production is induced by noxious stimuli such as oxidized LDL,² or as in this case, by mechanical forces.³ Lesion development is then propagated by chemokine-triggered leukocyte accumulation via two mechanisms, enhanced firm adhesion and chemotaxis. In the bloodstream, chemokines play a critical role in the initial step of leukocyte infiltration, within seconds converting leukocyte tethering or rolling on the vascular endothelium to firm arrest via the activation of leukocyte surface integrins.^4,5 As chemoattractants, chemokines subsequently play an important role in the directional migration of leukocytes through tissues.

Although chemokines were originally described for their role in host immunity, a growing body of evidence suggests a broader range of biological targets than was first appreciated. These data provide possible clues as to why CCR2-deficient animals . . . [Full Text of this Article]

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