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 chemoattractant 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 inducing O(2)(-) generation in circulating monocytes. Plasma levels of MCP-1 were measured before and 1, 5, 15, and 180 days after PTCA in 50 patients (30 males and 20 females, aged 62+/-5 years) who underwent PTCA and who had repeated angiograms at 6-month follow-up. Restenosis occurred in 14 (28%) patients. The MCP-1 level was no different at baseline between patients with or without restenosis. However, after the procedure, restenotic patients, compared with nonrestenotic patients, had statistically significant (P<0.0001) 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 after PTCA. Higher MCP-1 throughout the study was correlated with restenosis. Moreover, increased MCP-1 was significantly correlated with increased monocyte activity, as reflected by enhanced O(2)(-) generation. Finally, multivariate 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 production and macrophage accumulation in the balloon-injured vessel may play a pivotal role in restenosis after PTCA. MCP-1 may induce luminal renarrowing, at least in part, by inducing O(2)(-) release in monocytes. Further understanding of the mechanism(s) by which MCP-1 is produced and acts after arterial injury may provide insight into therapies to limit the progression of atherosclerosis and restenosis after balloon angioplasty.
Department of Medicine and Aging, University of Chieti "G D'Annunzio" School of Medicine, Chieti, Italy.
F
F
Cipollone
M
M
Marini
M
M
Fazia
B
B
Pini
A
A
Iezzi
M
M
Reale
L
L
Paloscia
G
G
Materazzo
E
E
D'Annunzio
P
P
Conti
F
F
Chiarelli
F
F
Cuccurullo
A
A
Mezzetti
D000368:Aged; D000704:Analysis of Variance; D015906:Angioplasty, Balloon, Coronary; D018932:Chemokine CCL2 / Q000097:blood*; D018946:Chemokine CCL5 / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000628:therapy; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012008:Recurrence; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors
D018932:Chemokine CCL2; D018946:Chemokine CCL5; D016209:Interleukin-8; D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate