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(Circulation. 2003;107:1958.)
© 2003 American Heart Association, Inc.

Brief Rapid Communications

Elevated Serum Levels of the CXCR3 Chemokine ITAC Are Associated With the Development of Transplant Coronary Artery Disease

John Kao, MD; Jon Kobashigawa, MD; Michael C. Fishbein, MD; W. Robb MacLellan, MD; Marie D. Burdick, BS; John A. Belperio, MD; Robert M. Strieter, MD

From the Department of Medicine, Division of Cardiology (J. Kao, J. Kobashigawa, W.R.M.); Department of Pathology (M.C.F.); and Departments of Medicine and Pathology, Division of Pulmonary Critical Care (M.D.B., J.A.B., R.M.S.), David Geffen School of Medicine at University of California, Los Angeles.

Correspondence to Dr Robert Strieter, Professor and Chief, Division of Pulmonary and Critical Care Medicine, Vice Chair of the Department of Medicine, Professor of Pathology, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, 900 Veteran Ave, 14-154 Warren Hall, Box 711922, Los Angeles CA 90024-1922. E-mail rstrieter{at}mednet.ucla.edu

Background— Human and animal studies of acute allograft rejection have implicated CCR5 and CXCR3 chemokines as causative factors. However these chemokines have not been assessed in transplant coronary artery disease (TCAD).

Methods and Results— Serum levels of chemokines were measured by ELISA. Levels of ITAC/CXCL11 were found to be elevated in patients with severe TCAD compared with long-term survivors of transplantation without TCAD and with healthy volunteers who had not undergone transplantation (1.476±0.274 ng/mL, 0.926±0.466 ng/mL, and 0.741±0.321 ng/mL, respectively; P<0.05 for all comparisons to TCAD group). Immunohistochemical localization confirmed the presence of CXCR3⁺ mononuclear cells within lesions and the presence of the ligand, ITAC/CXCL11, on the surface of endothelial cells associated with TCAD.

Conclusions— Elevated peripheral blood levels of the CXCR3 chemokine ITAC/CXCL11 are associated with severe TCAD and may serve as a marker for patients at increased risk for the development of this disease. Immunohistochemical localization of the CXCR3 chemokine ligand ITAC/CXCL11 on the endothelial surface of TCAD lesions with underlying infiltration of inflammatory mononuclear cells expressing CXCR3 suggests a causative role for this chemokine in the development of TCAD. The present study is one of the first to demonstrate a role for ITAC/CXCL11 in this disease.

Key Words: surgery • transplantation • cardiomyopathy • rejection • coronary disease

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