Investigating the role of macrophage-deposited collagen in the injured mouse heart

心脏病发作后会形成疤痕以防止心脏破裂。这种疤痕被认为是由一种叫做肌成纤维细胞的细胞产生的，这种细胞被进入的免疫细胞激活，然后沉积形成疤痕的蛋白质，比如胶原蛋白。我们已经证明，免疫细胞本身（巨噬细胞）可以直接为疤痕提供胶原蛋白，这种情况可能发生在心脏再生（斑马鱼，新生小鼠）和没有组织修复的永久性疤痕（成年小鼠，人类患者）。事实上，两种情况下的疤痕形式表明其成分不同，但尚未对此进行调查。我们建议使用电子显微镜分析新生小鼠和成年小鼠的疤痕，并确定损伤后再生和非再生小鼠心脏中哪些细胞与疤痕通信。我们将确定哪些巨噬细胞产生胶原蛋白，以及再生和非再生心脏中是否存在不同的胶原蛋白。最后，我们将敲除巨噬细胞中的胶原蛋白，以确定这种新型疤痕来源的功能。这项研究将提供对心脏病发作后疤痕形成的全面了解，并可能使我们能够修改疤痕作为人类患者的治疗方法。

After a heart attack a scar forms to prevent the heart from rupturing. This scar is thought to arise from a single cell type called myofibroblasts, whichbecome activated by incoming immune cells and then deposit scar-forming proteins such as collagens. We have shown that the immune cells themselves(macrophages) can contribute collagens directly to the scar and that this can happen in situations where the heart regenerates (zebrafish, neonatal mice)and when there is a permanent scar without tissue restoration (adult mice; human patients). The fact that scar forms during both settings suggest it is different in composition, yet this has not been investigated. We propose to analyse the scars in both neonatal and adult mice using electron microscopy and to determine which cells communicate with the scar in regenerating and non-regenerating mouse hearts following injury. We will determine which macrophages produce collagen and whether different collagens may be laid-down in regenerative versus non-regenerative hearts. Finally, we will knock-down collagens in macrophages to determine the function of this novel source of scar. This study will provide a comprehensive understanding of scar formation after heart attack and may enable us to modify scarring as a treatment for human patients.