Hypertension affects one-third of the world’s population, leading to cardiac dysfunction that is modulated by resident and recruited immune cells. Cardiomyocyte growth and increased cardiac mass are essential to withstand hypertensive stress; however, whether immune cells are involved in this compensatory cardioprotective process is unclear. In normotensive animals, single-cell transcriptomics of fate-mapped self-renewing cardiac resident macrophages (RMs) revealed transcriptionally diverse cell states with a core repertoire of reparative gene programs, including high expression of insulin-like growth factor-1 (Igf1). Hypertension drove selective in situ proliferation and transcriptional activation of some cardiac RM states, directly correlating with increased cardiomyocyte growth. During hypertension, inducible ablation of RMs or selective deletion of RM-derived Igf1 prevented adaptive cardiomyocyte growth, and cardiac mass failed to increase, which led to cardiac dysfunction. Single-cell transcriptomics identified a conserved IGF1-expressing macrophage subpopulation in human cardiomyopathy. Here we defined the absolute requirement of RM-produced IGF-1 in cardiac adaptation to hypertension.

高血压影响着世界三分之一的人口，导致心脏功能障碍，而心脏功能障碍是由常驻和招募的免疫细胞调节的。心肌细胞生长和心脏质量增加对于承受高血压应激至关重要；然而，免疫细胞是否参与这种代偿性心脏保护过程尚不清楚。在血压正常的动物中，命运图谱自我更新心脏驻留巨噬细胞 (RM) 的单细胞转录组学揭示了转录多样性的细胞状态，具有修复基因程序的核心库，包括胰岛素样生长因子 1 ( Igf1 ) 的高表达。高血压驱动一些心脏 RM 状态的选择性原位增殖和转录激活，与心肌细胞生长的增加直接相关。高血压期间，RMs的诱导消融或RM衍生的Igf1的选择性缺失阻止了心肌细胞的适应性生长，心脏质量未能增加，从而导致心功能障碍。单细胞转录组学鉴定了人类心肌病中保守的表达IGF1的巨噬细胞亚群。在这里，我们定义了心脏适应高血压过程中 RM 产生的 IGF-1 的绝对需求。