Colchicine Attenuates Microvascular Obstruction after Myocardial Ischemia-Reperfusion Injury by Inhibiting the Proliferation of Neutrophil in Bone Marrow

Complete and rapid recanalization of blood flow by percutaneous coronary intervention (PCI) is the most effective intervention for patients with ST-segment elevation myocardial infarction (STEMI). However, myocardial ischemia/reperfusion (I/R) injury leads to microvascular obstruction (MVO), limiting its efficacy. Colchicine can reduce myocardial I/R injury, but its effect on MVO is unclear. Hence, this study aimed to assess the role and mechanism of colchicine on MVO.Clinical data on STEMI patients with PCI were collected and risk factors related to MVO were analyzed. The rat myocardial I/R model was established to evaluate the MVO by thioflavin S staining. The myocardial I/R model of mice was treated with PBS or colchicine at the reperfusion. The effect of colchicine on cardiomyocyte apoptosis after I/R was evaluated by TUNEL and expression of cleaved caspase-3. ROS levels were detected in H9c2 cells to evaluate the colchicine effect on myocardial oxidative stress. Moreover, the mechanism through which colchicine attenuated MVO was examined using flow cytometry, WB, ELISA, immunohistochemistry, bioinformatics analysis, and immunofluorescence.Multivariate analysis showed that elevated neutrophils were associated with extensive MVO. Colchicine could attenuate MVO and reduce neutrophil recruitment and NETs formation after myocardial I/R. In addition, colchicine inhibited cardiomyocyte apoptosis in vivo and ROS levels in vitro. Furthermore, colchicine inhibited neutrophil proliferation in the bone marrow (BM) by inhibiting the S100A8/A9 inflammatory signaling pathway.Colchicine attenuated MVO after myocardial I/R injury by inhibiting the proliferation of neutrophils in BM through the neutrophil-derived S100A8/A9 inflammatory signaling pathway.