ESC Congress 2026 Abstract · Oct 26, 2026
Dapagliflozin attenuates post-infarction inflammation and remodeling via promoting metabolic reprogramming–driven cardiac lymphangiogenesis
By Zhang Z, Hao C, Chen L
Background: Persistent inflammation following myocardial infarction (MI) drives adverse ventricular remodeling and heart failure. Lymphangiogenesis is capable of speeding up inflammatory clearance. Pharmacological approaches targeting cardiac lymphatic remodeling remain limited. SGLT2 inhibitor Dapagliflozin(DAPA) could improve post-MI outcomes and exerts anti-inflammatory effects, the mechanistic pathways linking these observations remain unclear. We hypothesized that SGLT2 inhibition could promote Lymphangiogenesis and accelerate inflammatory resolution after MI. Methods: Plasma inflammatory cytokine levels were analyzed in MI patients with or without DAPA therapy. Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. Human lymphatic endothelial cells (LECs) were exposed to hypoxic conditions in vitro. DAPA was administered both in vivo and in vitro. Lymphangiogenesis, inflammatory cell clearance, and cardiac function were assessed using immunofluorescence, flow cytometry, lymphatic drainage assays, histological staining, and echocardiography in MI mice. Transcriptomic and metabolomic profiling were performed to explore molecular mechanisms. Results: Three-dimensional reconstruction together with Western blot, RT-qPCR, and immunofluorescence analyses demonstrated that DAPA markedly enhanced structural remodeling of the cardiac lymphatic network, characterized by increased LEC density, enlarged lymphatic lumen diameter, and enhanced branching in the infarct border zone. Increased lymphangiogenesis is associated with accelerated clearance of inflammatory macrophages and pro-inflammatory cytokines, resulting in reduced myocardial edema. Histological analyses (H&E and Masson staining) revealed attenuated inflammatory infiltration and myocardial fibrosis in DAPA-treated mice. Consistently, echocardiography showed improved left ventricular ejection fraction and reduced ventricular dilation after MI. Transcriptomic analysis revealed significant enrichment of MAPK/ERK signaling, cell-cycle regulation, and lymphangiogenesis-associated pathways. Metabolomic profiling demonstrated a metabolic shift characterized by enhanced oxidative phosphorylation and tricarboxylic acid (TCA) cycle activity, together with improved mitochondrial energetic capacity. These coordinated transcriptional and metabolic adaptations indicate that DAPA reprograms lymphatic endothelial cell metabolism and attenuates post-MI inflammation and remodeling Conclusions: Dapagliflozin promotes post-infarction cardiac lymphatic remodeling, thereby accelerating inflammatory resolution and functional recovery. These findings highlight pharmacological enhancement of cardiac lymphangiogenesis as a promising therapeutic strategy.Dapagliflozin Promotes Post-MI Cardiac Repair