Abstract: TH-PO0270
GLP-1 Receptor Agonist Therapy Shields the Heart from Renal Fibrosis in Cardiorenal Syndrome
Session Information
- Hypertension and CVD: Mechanisms
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Lee, Chia Ying, National Taiwan University College of Medicine, Taipei City, Taiwan
- See, Daniel H. W., National Taiwan University College of Medicine, Taipei City, Taiwan
- Huang, Yue-Jhu, National Taiwan University Hospital, Taipei City, Taiwan
- Liu, Shin Yun, National Taiwan University Cancer Center, Taipei City, Taiwan
- Huang, Jenq-wen, National Taiwan University College of Medicine, Taipei City, Taiwan
- Su, Chi-Ting, National Taiwan University College of Medicine, Taipei City, Taiwan
Background
Cardiorenal syndrome reflects the bidirectional interplay between cardiac and renal dysfunction. While GLP-1 receptor agonists are established in metabolic and cardiovascular care, their potential to mitigate renal injury–induced cardiomyopathy remains underexplored. RNA sequencing of cardiac tissue from CKD mice revealed upregulation of GLP-1 receptors, prompting investigation into liraglutide’s role in modulating CKD-related cardiac remodeling and dysfunction.
Methods
CKD was induced in 9-week-old C57BL/6 mice via adenine-enriched diets, leading to progressive renal fibrosis. Mice received either vehicle or liraglutide (1 mg/kg/day). Glomerular filtration rate was monitored longitudinally using transdermal GFR technology (MediBeacon), and cardiac function was assessed using high-frequency echocardiography (Vevo 2100). In parallel, cardiomyocytes (CMs) derived from human induced pluripotent stem cells (hiPSCs) were exposed to pooled serum from CKD patients to model uremic cardiotoxicity. Outcomes included inflammatory signaling (IL-6, TNF-α, VCAM-1), ROS production, apoptosis (Annexin V, PI), and contractility assessed by microelectrode array (MEA, Maestro Edge).
Results
CKD mice demonstrated impaired LV function and elevated expression of fibrotic and inflammatory markers (fibronectin, TNF-α, IL-10, VCAM-1; all p<0.001). Liraglutide treatment improved LV function, reduced cardiac fibrosis, and significantly suppressed these pathological markers (p<0.001). Electron microscopy showed reversal of mitochondrial fragmentation in liraglutide-treated hearts. In vitro, CMs exposed to CKD serum showed increased ROS production, apoptosis, and reduced contractility. Liraglutide co-treatment suppressed ROS and apoptotic markers and partially restored CM contractility. Pro-inflammatory cytokine expression in CMs was also reduced.
Conclusion
Liraglutide confers cardioprotection in the context of CKD by targeting multiple injury pathways—including inflammation, fibrosis, oxidative stress, and mitochondrial integrity. These preclinical findings provide mechanistic and translational support for the therapeutic potential of GLP-1 receptor agonists in cardiorenal syndrome and warrant further clinical investigation.