P152	Correlation between the surface expression of monocyte chemoattractant protein-1 receptor and arteriogenic responsiveness of monocytes in patients with coronary artery disease.
1S.Vöö, 2M.Lenter, 1F.Czepluch, 1J.Waltenberger
1Department of Cardiology, University of Maastricht/ Cardiovascular Research Institute of Maastricht, Maastricht, NL; 2Department of Pulmonary Research, Genomics Group, Boehringer Ingelheim Pharma GmbH&Co.KG, Biberach an der Riss, DE.

Monocytes are important cellular participants in the process of vascular growth and thus may contribute to the clinical recovery after regional ischemia. Their transmigration through endothelium towards an ischemic area is a critical step in this scenario and is promoted by local release of monocyte chemoattractant protein-1 (MCP-1) acting through CCR2 receptor. Therefore, we investigated the role of MCP-1/CCR2 system in transmigration of monocytes from patients with coronary artery disease (CAD) and in healthy subjects. Monocytes were isolated from 8 patients with CAD and 5 control subjects (no ischemic disease) by an immunomagnetic system. The migratory response towards MCP-1 (10 ng/mL) was quantified by transmembrane chemotaxis assay. The presence of CCR2 on cell surface was evaluated by flow cytometry. MCP-1-induced Ca2+ release was quantified by Fluo-4 fluorometric imaging. The chemotactic response of monocytes towards MCP-1 was significantly decreased in CAD patients compared to controls (116±4.7% versus 148±3.3%; p< 0.05). Likewise, the percentage of CCR2-positive monocytes was lower in CAD in comparison to control subjects (p<0.05). Moreover, CCR2-positive monocytes from CAD displayed a lower density of CCR2 on plasma membrane than in controls (27.8±5.9 versus 45.5±7.9 specific mean fluorescent intensity; p<0.05). Monocytes from CAD were less sensitive to MCP-1 with respect to Ca2+ release (EC50 43.0±14.2 nM versus 18.7±5.7 nM in controls; p<0.05). Taken together, the monocyte response towards MCP-1 is attenuated in CAD patients. This correlates with a reduced expression of MCP-1 receptor on plasma membrane which provides a molecular explanation for their functional impairment. When put into a clinical perspective, the use of MCP-1 for therapeutic arteriogenesis might be limited by the reduced responsiveness of monocytes.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.