Elevated Circulating Levels of Monocyte Chemoattractant Protein-1 in Patients With Restenosis After Coronary Angioplasty

Chemoattractant Protein-1 in Patients With Restenosis After Coronary Angioplasty To the Editor: We read with great interest the article by Cipollone et al1 on the expression of monocyte chemoattractant protein-1 (MCP-1) after percutaneous transluminal coronary angioplasty (PTCA). In their study, plasma MCP-1 levels were significantly increased 1 day after PTCA, and patients with restenosis showed significantly higher MCP-1 levels after PTCA than those without restenosis. Several previous studies, including our own, have revealed that PTCA induces inflammatory responses.2 In addition, we reported that MCP-1 is expressed in human atherosclerotic lesions3 and that the interaction between monocytes and endothelial cells induces MCP-1 expression and enhances monocyte migration.4,5 Therefore, like Cipollone et al,1 we hypothesized that MCP-1 played important roles in restenosis after intervention. To prove our hypothesis, we examined 40 patients with angina pectoris who underwent elective PTCA for isolated stenotic lesions of the left coronary artery.6 A 5F Amplatz catheter was placed in the coronary sinus, and blood samples were obtained through the catheter before, immediately after, and 4 and 24 hours after angioplasty. Blood samples were also obtained from the femoral artery 24 hours after angioplasty. Plasma levels of MCP-1 and macrophagecolony stimulating factor (M-CSF) were measured by specific enzyme immunoassays. M-CSF levels in the coronary sinus blood showed a significant increase 4 and 24 hours after PTCA (from [mean6SD] 671651 to 942663 and to 1220679 pg/mL, respectively). In the femoral arterial blood, a slight increase in M-CSF levels was found 24 hours after PTCA; however, the difference was not significant (from 6816135 to 8656156 pg/mL, P50.155). On the other hand, MCP-1 levels in the coronary sinus blood did not change significantly 4 and 24 hours after PTCA (from 441659 to 424636 and to 457645 pg/mL, respectively) and also in the femoral artery blood 24 hours after PTCA (from 469687 to 451676 pg/mL). We performed follow-up coronary angiography after 6 months; M-CSF levels in the coronary sinus blood 24 hours after PTCA in patients with restenosis were significantly higher than those in patients without restenosis (14706133 vs 10616110 pg/mL, P,0.05). A significant positive correlation was observed between M-CSF levels and loss index (r50.59, P,0.01). M-CSF promotes proliferation, differentiation, and migration of mononuclear phagocytes and has been reported to be associated with the early development of atherosclerosis. Saitoh et al7 assessed the relation between the plasma concentration of M-CSF and the incidence of acute coronary events in patients with coronary artery disease and found that an increased circulating M-CSF concentration reflected atherosclerotic progression and predicted future cardiac events. Mozes et al8 demonstrated that gene transfer of complemental DNA encoding human M-CSF in the rabbit artery induced local infiltration of smooth muscle cells and macrophages. Their findings along with our observations suggest that M-CSF, rather than MCP-1, expressed locally in the coronary artery plays primary roles in the pathogenesis of restenosis after PTCA. In contrast to the study by Cipollone et al,1 we did not find any significant increase in MCP-1 levels in the coronary sinus and femoral artery blood during a 24-hour observation period. However, we could not exclude the possibility that MCP-1 expression occurred rather later after PTCA, because M-CSF has been shown to stimulate MCP-1 expression in endothelial cells.