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

Figure 3 Mechanism-targeted therapeutic strategies for cardio-hepatic crosstalk in metabolic dysfunction-associated steatotic liver disease. Central panel: Bidirectional cardio-hepatic pathogenic signalling loops. Four therapeutic modules encircle the core: (1) Upper left: Agents blocking liver-derived pathogenic mediators; (2) Upper right: Therapies reversing heart-induced hepatic injury; (3) Lower left: Interventions suppressing systemic amplification pathways; (4) Lower right: Synergistic combination regimens. Key therapeutic agents are listed within each corresponding module. Full molecular mediators are detailed in Table 1; evidence grading of each intervention is summarised in Table 2. GLP-1: Glucagon-like peptide-1; GIP: Glucose-dependent insulinotropic polypeptide; THR-β: Thyroid hormone receptor-β; pan-PPAR: Pan-peroxisome proliferator-activated receptor; PPARγ: Peroxisome proliferator-activated receptor-γ; FGF21: Fibroblast growth factor 21; PCSK9: Proprotein convertase subtilisin/kexin type 9; EVs: Extracellular vesicles; SGLT2: Sodium-glucose cotransporter 2; RAAS: Renin-angiotensin-aldosterone system; ACEI: Angiotensin-converting enzyme inhibitor; ARB: Angiotensin II receptor blocker; MRA: Mineralocorticoid receptor antagonist; GLP-1RA: Glucagon-like peptide-1 receptor agonist; SGLT2i: Sodium-glucose cotransporter 2 inhibitor; FXR: Farnesoid X receptor; RNAi: RNA interference; PNPLA3: Patatin-like phospholipase domain-containing protein 3; HSD17β13: Hydroxysteroid 17-beta dehydrogenase 13.