Elevated circulating levels of monocyte chemoattractant protein-1 in patients with restenosis after coronary angioplasty

Inflammation plays a pathogenic role in the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA), Monocyte chemoattra ctant protein-1 (MCP-1) is a potent chemoattractant of monocytes; however, its role in the pathophysiology of restenosis is still unclear. We set out to investigate the role of MCP-1 in restenosis after PTCA. In addition, we tested the hypothesis that MCP-1 exerts its effect, at least in part, by in ducing O-2(-) generation in circulating monocytes. Plasma levels of MCP-1 w ere measured before and 1, 5, 15, and 180 days after PTCA in 50 patients (3 0 males and 20 females, aged 62+/-5 years) who underwent PTCA and who had r epeated angiograms at 6-month follow-up. Restenosis occurred in 14 (28%) pa tients. The MCP-1 level was no different at baseline between patients with or without restenosis. However, after the procedure, restenotic patients, c ompared with nonrestenotic patients, had statistically significant (P<0.000 1) elevated levels of MCP-1. In contrast, plasma levels of other chemokines , such as RANTES and interleukin-8, did not differ between the 2 groups aft er PTCA. Higher MCP-1 throughout the study was correlated with restenosis. Moreover, increased MCP-1 was significantly correlated with increased monoc yte activity, as reflected by enhanced O-2(-) generation Finally, multivari ate regression analysis showed that the MCP-1 plasma level measured 15 days after PTCA was the only statistically significant independent predictor of restenosis (beta =0.688, P<0.0001). This study suggests that MCP-1 product ion and macrophage accumulation in the balloon-injured vessel may play a pi votal role in restenosis after PTCA. MCP-1 may induce luminal renarrowing, at least in part, by inducing O-2(-) release in monocytes. Further understa nding of the mechanism(s) by which MCP-1 is produced and acts after arteria l injury may provide insight into therapies to limit the progression of ath erosclerosis and restenosis after balloon angioplasty.