Cardio-hepatic axis in metabolic dysfunction-associated steatotic liver disease: Mechanisms, clinical implications and therapeutic opportunities

Figure 1 Schematic diagram of bidirectional crosstalk and systemic regulatory networks in the cardio-hepatic axis in metabolic dysfunction-associated steatotic liver disease. The central white circle illustrates the direct bidirectional dialogue between the liver and the heart: The liver acts on the heart through extracellular vesicles, while the heart reciprocally regulates the liver through the secretion of atrial natriuretic peptide and B-type natriuretic peptide, accompanied by target organ phenotypes. The grey annular band encircling the core region summarizes the pathogenic mediators intertwined with the systemic amplification networks that drive shared core pathways underlying concurrent cardiac and hepatic injury. The outermost four modules, immunometabolic network, gut signaling network, circadian rhythm network, and genetic/epigenetic/CHIP, further exacerbate the vicious cycle of the cardio-hepatic axis by amplifying pathological molecular levels within the loop. For a detailed list of all specific molecules mediating these interactions, see Table 1. PCSK9: Proprotein convertase subtilisin/kexin type 9; FXI: Factor XI; FGF21: Fibroblast growth factor 21; ANGPTL3: Angiopoietin-like protein 3; SAA1/4: Serum amyloid A1/A4; EVs: Extracellular vesicles; ANP: Atrial natriuretic peptide; BNP: B-type natriuretic peptide; HSC: Hepatic stellate cell; MASH: Metabolic-dysfunction-associated steatohepatitis; AngII: Angiotensin II; GDF15: Growth differentiation factor 15; CHIP: Clonal hematopoiesis of indeterminate potential.