Sen Melodi G, Chooi Roger, McMullen Julie R
Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
Heart Research Institute, Newtown, New South Wales, Australia.
J Physiol. 2025 Jan 31. doi: 10.1113/JP287400.
Cardiovascular disease affects millions of people worldwide and often presents with other conditions including metabolic, renal and neurological disorders. A variety of secreted factors from multiple organs/tissues (proteins, nucleic acids and lipids) have been implicated in facilitating organ cross-talk that may contribute to the development of multimorbidity. Secreted proteins have received the most attention, with the greatest body of research related to factors released from adipose tissue (adipokines), followed by skeletal muscle (myokines). To date, there have been fewer studies on proteins released from the heart (cardiokines) implicated with organ cross-talk. Early evidence for the secretion of cardiac-specific factors facilitating organ cross-talk came in the form of natriuretic peptides which are secreted via the classical endoplasmic reticulum-Golgi pathway. More recently, studies in cardiomyocyte-specific genetic mouse models have revealed cardiac-initiated organ cross-talk. Cardiomyocyte-specific modulation of microRNAs (miR-208a and miR-23-27-24 cluster) and proteins such as the mediator complex subunit 13 (MED13), G-protein-coupled receptor kinase 2 (GRK2), mutant α-myosin heavy-chain (αMHC), ubiquitin-like modifier-activating enzyme (ATG7), oestrogen receptor alpha (ERα) and fibroblast growth factor 21 (FGF21) have resulted in metabolic and renal phenotypes. These studies have implicated a variety of factors which can be secreted via the classical pathway or via non-classical mechanisms including the release of extracellular vesicles. Cross-talk between the heart and the brain has also been described (e.g. via miR-1 and an emerging concept, interoception: detection of internal neural signals). Here we summarize these studies taking into consideration that factors may be secreted in both settings of health and in disease.
心血管疾病影响着全球数百万人，并且常常伴有其他病症，包括代谢、肾脏和神经紊乱。多个器官/组织分泌的多种因子（蛋白质、核酸和脂质）参与促进器官间的相互作用，这可能导致多种疾病的发生。分泌蛋白受到了最多关注，其中关于脂肪组织分泌因子（脂肪因子）的研究最多，其次是骨骼肌分泌因子（肌动蛋白）。迄今为止，关于心脏分泌的与器官间相互作用有关的蛋白质（心脏因子）的研究较少。促进器官间相互作用的心脏特异性因子分泌的早期证据是以利钠肽的形式出现的，利钠肽通过经典的内质网-高尔基体途径分泌。最近，对心肌细胞特异性基因小鼠模型的研究揭示了心脏引发的器官间相互作用。心肌细胞特异性调节微小RNA（miR-208a和miR-23-27-24簇）以及蛋白质，如中介体复合物亚基13（MED13）、G蛋白偶联受体激酶2（GRK2）、突变型α-肌球蛋白重链（αMHC）、泛素样修饰激活酶（ATG7）、雌激素受体α（ERα）和成纤维细胞生长因子21（FGF21），已导致代谢和肾脏表型。这些研究涉及多种可通过经典途径或非经典机制分泌的因子，包括细胞外囊泡的释放。心脏与大脑之间的相互作用也有描述（例如通过miR-1和一个新兴概念——内感受：内部神经信号的检测）。在此，我们总结这些研究，同时考虑到这些因子可能在健康和疾病状态下均有分泌。
