Abstract 10899: Matrix Metalloproteinase-9 Might Contribute to Mobilization of Bone Marrow-Derived Cells After Coronary Stent Implantation
After vascular injury such as stent implantation, it has been suggested that the inflammatory response triggers mobilization of bone marrow-derived stem cells including both endothelial and smooth muscle progenitor cells, leading to re-endothelialization as well as restenoisis.. It has been postulated that neutrophil-released matrix metalloproteinase-9 (MMP-9) induces stem cell mobilization. To elucidate the mechanistic linkage between inflammation and stem cell mobilization, we serially measured circulating CD34-positive mononuclear cells, binding of 8B2, an antibody recognizing activation dependent neoepitope of integrin Mac-1, on the surface of neutrophils and active matrix metalloproteinase (MMP)-9 levels in 30 patients undergoing coronary stenting. After implantation of bare-metal stents, significant increases in the number of CD34-positive cells (maximum at the day 7, P<0.001), 8B2 binding (at 48 h, P<0.001), and active MMP-9 level (at 24 h, P<0.001) were observed. However, these changes were absent after implantation of sirolimus-eluting stents. In all patients, MMP-9 level at 24 h was correlated with the number of CD34-positive cells at day 7 (R=0.38, P<0.05) as well as 8B2 binding at 48 h (R=0.42, P<0.01). In patients who were implanted bare-metal stents, multiple regression analysis showed that angiographic late lumen loss was independently predicted by the number of CD34-positive cells at day 7 (R=34, P<0.05), 8B2 binding at 48 h (R=0.38, P<0.01), and MMP-9 levels at 24 h (R=0.32, P<0.05). In human isolated neutrophils taken from 5 healthy volunteers, stimulation of Mac-1 neoepitope by 8B2 antibody induced activated MMP-9 peoduction more than isotype control (P<0.01). Vascular injury by stent implantation may locally produce MMP-9, possibly leading to mobilization of bone marrow-derived stem cells, and subsequently to restenosis. Activation of neutrophil Mac-1 may greatly contribute to MMP-9 production. Excessive inhibition of these reactions by drug-eluting stents raise novel issues of present drug-eluting stents such as re-endothelialization failure.
- © 2011 by American Heart Association, Inc.