Up-regulation of ANXA1 suppresses polymorphonuclear neutrophil infiltration and myeloperoxidase activity by activating STAT3 signaling pathway in rat models of myocardial ischemia-reperfusion injury.
Cell Signal. 2019 10;62:109325
Authors: Zhao C, Zhang B, Jiang J, Wang Y, Wu Y
Myocardial ischemia-reperfusion injury (MIRI) is recognized as a major cause of morbidity and mortality which is commonly associated with coronary artery disease. In recent studies, annexin A1 gene (ANXA1) has been discovered to be involved in the treatment for MIRI. In this study, the primary focus was on the molecular mechanism of ANXA1 in polymorphonuclear neutrophil (PMN) infiltration and myeloperoxidase (MPO) activity in rats with MIRI. Initially, microarray analysis was carried out in order to identify differentially expressed genes. Moreover, a rat model of MIRI was established for evaluating the expression of ANXA1, signal transducer and activator of transcription 3 (STAT3) and vascular endothelial growth factor (VEGF) in myocardial tissues. Following this, the ANXA1 vector, siRNA-ANXA1, and Stattic (inhibitor of STAT3 signaling pathway) were utilized for analyzing the regulatory role of ANXA1 in physiological indexes, hemodynamic parameters, inflammatory factors, myocardial infarct size, MPO activity, PMN infiltration, and apoptosis of PMNs. Furthermore, the relationship between ANXA1 and STAT3 signaling pathway was analyzed. Initially, a reduction in the expression of ANXA1, STAT3 and VEGF in myocardial tissues of MIRI rats was found. To elaborate, overexpressed ANXA1 inhibited levels of inflammatory factors, the activation of PMN infiltration, reduced the degree of PMN infiltration, and decreased the apoptosis of PMNs. More importantly, down-regulated ANXA1 inhibited the activation of STAT3 signaling pathway, which thereby suppressed VEGF expression. With this all taken into account, the present study presents that up-regulated ANXA1 inhibits PMN infiltration and MPO activity by activation of STAT3 signaling pathway in rats with MIRI.
PMID: 31132398 [PubMed - indexed for MEDLINE]