Neutrophil Polarization Following Myocardial Infarction

摘要 大约四分之一的心肌梗死(MI)患者进展为充血性心力衰竭， 它的5年死亡率为50%。本项目的目标是了解心梗后的角色 通过建立这种细胞类型在伤口愈合过程中如何在表型上转换的中性粒细胞 从炎症到修复。我们假设中性粒细胞经历一种时间表型 包括影响心肌梗死后炎症消退和ECM组织的演变。 具体目标1将绘制心肌梗塞后时间进程中的中性粒细胞极化表型。目标2将 验证中性粒细胞积极促进炎症消退的假设。目标3将测试 中性粒细胞在瘢痕形成中积极促进细胞外基质组织的假说 队形。创新在于对心肌梗塞后中性粒细胞亚型的评估，这将使我们能够 将早期中性粒细胞生理学与晚期重塑结果联系起来。多学科方法将 探索中性粒细胞调节重塑的机制。这项研究将 推动对左心室重构细胞基础的理解，并确定新的干预措施 目标指向中性粒细胞。

Abstract About one in four myocardial infarction (MI) patients progress to develop congestive heart failure, which has a 5-year mortality rate of 50%. The goal of this project is to understand post-MI roles of neutrophils by establishing how this cell type transitions in phenotype during wound healing spanning from inflammation to repair. We hypothesize that neutrophils undergo a temporal phenotype evolution that includes influencing post-MI inflammation resolution and ECM organization. Specific aim 1 will map neutrophil polarization phenotypes over the post-MI time course. Aim 2 will test the hypothesis that neutrophils actively contribute to inflammation resolution. Aim 3 will test the hypothesis that neutrophils actively contribute to extracellular matrix organization during scar formation. Innovation lies in the evaluation of neutrophil subtypes post-MI, which will allow us to connect early neutrophil cell physiology to late remodeling outcomes. Multi-discipline approaches will be integrated to explore the mechanisms whereby neutrophils regulate remodeling. This study will drive forward the understanding of the cellular basis of LV remodeling and identify novel intervention targets directed at neutrophils.