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.
Cipollone
F
F
Department of Medicine and Aging, University of Chieti "G D'Annunzio" School of Medicine, Chieti, Italy.
Marini
M
M
Fazia
M
M
Pini
B
B
Iezzi
A
A
Reale
M
M
Paloscia
L
L
Materazzo
G
G
D'Annunzio
E
E
Conti
P
P
Chiarelli
F
F
Cuccurullo
F
F
Mezzetti
A
A
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