Conclusion
Our results illustrate a novel mechanism by which HMGB1, derived mainly from PMPs, plays a crucial role in the pathogenesis of no-reflow, revealing a novel therapeutic target.
Methods
44 STEMI patients undergoing successful primary percutaneous coronary intervention (PCI) were included in our study. Plasma HMGB1 levels in both the peripheral artery (PA) and infarct-related coronary artery (IRA) were measured by ELISA. Flow cytometry and confocal microscopy assessed the level of HMGB1+ platelet derived microparticles (PMPs) and platelet activation. Flow cytometry and western blot evaluated the procoagulant activity (PCA) and the release of inflammatory factors of human microvascular endothelial cells (HCEMCs).
Results
HMGB1 levels were significantly higher in the IRA in no-reflow patients. The levels of HMGB1+ PMPs were considerably higher in the IRA of patients with no reflow and were strongly associated with platelet activation. Moreover, our results show that HMGB1 interacts with human microvascular endothelial cells primarily through TLR4, inducing HCMEC proinflammatory, procoagulant phenotype, and monocyte recruitment, accelerating microvascular obstruction and facilitating the development of no reflow.