Immune Response-Mediated Regulation of Cardiomyocyte Growth and Renewal

心力衰竭进展是一个复杂的生物过程，由适应性不良的心肌细胞引起。 对损伤的反应，再加上成人心脏不能替换丢失或受损的心肌细胞。 可以想象，确定控制这两个看似不相关的过程的共同途径将 对预防甚至逆转心力衰竭进展的治疗策略产生深远影响。数不胜数 提议的财团成员和其他人的观察支持这样一种观点，即内生的 新生哺乳动物心脏的增殖能力在出生后早期就会减弱，从 心肌细胞发生从肥大到肥大的生长。拟议财团的成员和 其他人此前也证明了与免疫反应激活有关的机制可能起作用。 在心肌细胞肥大、死亡、愈合甚至刺激新的心肌细胞生成方面起作用。这个 目前的提案汇集了几个在免疫学、心肌学方面具有重要专业知识的团体 重塑、肥大和再生，总体目标是确定免疫反应的作用 心脏生长、愈合和再生的调控信号。事实上，免疫反应已经采取了 在过去的几年中处于中心阶段，是心脏健康老化和康复的主要决定因素 伤害，以及慢性病的决定因素，当它受到不适当的监管时，它就会出现。因此，这一点 计划项目将调查涉及交叉点的前沿和新兴科学调查领域 在免疫系统和心肌之间。具体地说，研究将检查先天免疫的作用 反应信号在心肌细胞周期调节，以及在心肌重构和肥厚。 此外，专门的研究将检查cGAS-sting在心肌细胞和心肌细胞中表达的作用。 免疫细胞在心脏生长和再生调节中的作用。最后，在建议方案项目中进行研究 将研究巨噬细胞亚型在介导心肌对细胞治疗和损伤的反应中的作用。 拟议的方案项目很好地符合网络中各小组的兴趣和专业知识 将他们的重点扩展到高度相关但探索不足的心脏病理生理学领域。海流 建议书为计划项目中的所有小组创建了一个新的共同重点，旨在建立一个新的 该领域的范例。

Heart failure progression is a complex biological process that is precipitated by the maladaptive myocardial response to injury, compounded by failure of the adult heart to replace lost or damaged cardiomyocytes. Conceivably, identifying common pathways that regulate these two seemingly unrelated processes would profoundly impact therapeutic strategies to prevent, and even reverse heart failure progression. Numerous observations by members of the proposed consortium and others support the notion that the endogenous capacity of the neonatal mammalian heart to proliferate fades in the early postnatal life as a switch from hyperplastic to hypertrophic growth of cardiomyocytes takes place. Members of the proposed consortium and others have also previously demonstrated that mechanisms linked to activation of immune response may play a role in cardiomyocyte hypertrophy, death, healing and even stimulation of new cardiomyocyte generation. The current proposal brings together several groups with significant expertise in immunology, myocardial remodeling, hypertrophy and regeneration with the overall goal of determining the role of immune response signaling in regulation of cardiac growth, healing and regeneration. Indeed, the immune response has taken center stage in the past several years as a primary determinant of both healthy cardiac aging and healing after injury, as well as a determinant of chronic disease states when it is inappropriately regulated. Thus, this Program Project will investigate a frontier and emerging area of scientific investigation involving the intersection between the immune system and the myocardium. Specifically, studies will examine the role of innate immune response signals in cardiomyocyte cell cycle regulation, as well as in myocardial remodeling and hypertrophy. In addition, dedicated studies will examine the role of cGAS-STING expression in cardiomyocytes and in immune cells in regulation of cardiac growth and regeneration. Finally, studies in the proposed Program Project will examine the role of macrophage subtypes in mediating myocardial response to cell therapy as well as injury. The proposed Program Project is well in line with the interest and expertise of the groups in the network and extends their focus into a highly relevant and poorly explored area of cardiac pathophysiology. The current proposal creates a new shared focus for all the groups in the Program Project that aims to establish a new paradigm in the field.