Decoding cardiorenal crosstalk: Intercellular communication mechanisms and therapeutic insights in cardiorenal syndrome

Figures

• 

  Figure 1. Modes of intercellular communication Left (secretory-factor-mediated cell communication): this is the most classic form of cell communication: endocrine cells secrete hormones that travel through the bloodstream to act on target cells at a distance; paracrine cells release growth factors to locally regulate neighboring cells; and autocrine cells use cytokines to regulate their own signaling. These three types of secretory signals work together to coordinate physiological activities throughout the body and at the local level. Middle (exosome-mediated cell communication): cells secrete exosomes—vesicles containing lipids, proteins, and nucleic acids—to safely deliver signaling molecules to target cells, enabling long-distance, precise information transfer. This process plays a critical role in disease regulation and tissue repair. Right (extracellular-matrix-mediated cell-cell communication): cells bind to the extracellular matrix (collagen, laminin, etc.) via surface integrins. The matrix simultaneously stores and releases growth factors such as VEGF, establishing bidirectional signaling between cells and their microenvironment. This regulates cell adhesion, proliferation, and…

• 

  Figure 2. Signaling-molecule-mediated heart-kidney communication This figure summarizes the bidirectional damage communication mechanism between the heart and kidneys in cardiorenal syndrome, which is mediated by various signaling molecules including inflammatory factors, vasoactive factors, chemokines, myokines, and adrenomedullin. It systematically illustrates the pathological damage pathways of CRS mediated by these signaling molecules.

• 

  Figure 3. Extracellular-vesicle-mediated heart-kidney communication This figure systematically illustrates the extracellular vesicles secreted by various cell types (cardiomyocytes, renal tubular epithelial cells, and macrophages), which mediate bidirectional communication between the heart and kidneys by carrying miRNAs, proteins, and other molecules, thereby contributing to the pathological damage associated with cardiorenal syndrome.

• 

  Figure 4. Extracellular-matrix-mediated heart-kidney communication This figure illustrates how an imbalance in extracellular matrix homeostasis (disrupted degradation mediated by MMP-9 and abnormal cell-matrix communication mediated by integrins) contributes to bidirectional damage to both the heart and kidneys through pathways such as inflammation and fibrosis, thereby playing a central role in the pathogenesis and progression of cardiorenal syndrome.