Activation of matrix metalloproteinase-9 is associated with mobilization of bone marrow-derived cells after coronary stent implantation

BackgroundAfter stent-related vascular injury, an inflammatory response triggers the mobilization of bone marrow-derived stem cells, including both endothelial and smooth muscle progenitors, leading to re-endothelialization as well as restenosis. It has been postulated that neutrophil-released matrix metalloproteinase-9 (MMP-9) induces stem cell mobilization.AimTo elucidate the mechanistic link between inflammation and stem cell mobilization after coronary stenting.MethodsIn 31 patients undergoing coronary stenting, we serially measured activated Mac-1 on the surface of neutrophils and active MMP-9 levels in the coronary sinus blood plasma, and the number of circulating CD34-positive cells in the peripheral blood.ResultsAfter bare-metal stent implantation (n = 21), significant increases in the numbers of CD34-positive cells (maximum on post-procedure day 7, P < 0.001), activated Mac-1 (at 48 h, P < 0.001), and active MMP-9 levels (at 24 h, P < 0.001) were observed. However, these changes were absent after sirolimus-eluting stent implantation (n = 10). In overall patients, the numbers of CD34-positive cells on day 7 (R = 0.58, P < 0.01) and activated Mac-1 at 48 h (R = 0.58, P < 0.01) were both correlated with active MMP-9 levels at 24 h. Stimulation of activated Mac-1 on the surface of isolated human neutrophils produced active MMP-9 release in vitro.ConclusionsThese results suggest that stent-induced activation of Mac-1 on the surface of neutrophils might trigger their MMP-9 release, possibly leading to the mobilization of bone marrow-derived stem cells. These reactions were substantially inhibited by sirolimus-eluting stents.