Abstract: TH-OR81
Glucagon-Like Peptide 1 Receptor Agonist Attenuates Cardiovascular Injury Caused by Renal Fibrosis
Session Information
- Hypertension and CVD: Research Advances
October 24, 2024 | Location: Room 5, Convention Center
Abstract Time: 05:50 PM - 06:00 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Tsai, Ping-Chi, National Taiwan University Hospital, Taipei, Taiwan
- See, Daniel H. W., National Taiwan University Hospital, Taipei, Taiwan
- Huang, Yue-Jhu, National Taiwan University Hospital, Taipei, Taiwan
- Liu, Shin Yun, National Taiwan University Cancer Center, Taipei, Taiwan
- Huang, Jenq-wen, National Taiwan University Hospital, Taipei, Taiwan
- Su, Chi-Ting, National Taiwan University Cancer Center, Taipei, Taiwan
Background
The term “cardiorenal syndrome” has been coined to describe the condition in which a disorder of either the heart or kidneys affects the other organ. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog that acts as a GLP-1 receptor agonist (GLP-1RA) , exerts cardioprotective effects. We hypothesized that liraglutide treatment could alleviate secondary damage to the heart stemming from chronic kidney disease (CKD).
Methods
We fed adenine to C57BL/6 mice at the age of 9 weeks (CKD mice) to induce renal fibrosis. Renal function was evaluated using a Transdermal GFR Measurement System (MediBeacon) before, during, and after adenine feeding, with or without liraglutide, at a dose of 1 mg/kg/day. A Prospect High-Frequency Ultrasound Imaging System was used to evaluate left ventricular function. Mitochondrial function, fibrotic markers and caspase activity were studied to understand the molecular pathology in cardiac tissue. We used NHCF-V human cardiac fibroblasts (HCFs) to investigate cellular respiration by use of a Seahorse XF Analyser. Conditional media (CM) collected from hypoxic human proximal tubule (HK-2) cells were used to treat HCFs to determine reactive oxidative species (ROS) levels, inflammatory signaling and apoptosis.
Results
The echocardiography results revealed poorer ejection fraction (EF) in adenine-fed mice than in wild-type mice, which could be abrogated by liraglutide treatment (EF: 43% vs. 55%; p<0.001). Cardiac tissue showed higher levels of inflammatory markers (TNF-α, IL-10, VCAM-1; p<0.001) in CKD mice, with liraglutide treatment reducing the levels of these markers (p<0.001). Moreover, HCFs expressed high levels of ROS and apoptotic markers when treated with CM of hypoxic HK-2, based on results of flow cytometry assays. Liraglutide treatment reduced said oxidative stress and apoptosis. ATP production and glycolysis tended to be lower in the HCFs stressed with CM of hypoxic HK-2, and this reduction was partially reversed with liraglutide.
Conclusion
Our findings showed that renal fibrosis negatively impacts the heart. We demonstrated that GLP-1RA attenuated the damage to the heart caused by CKD to some degree. This cardioprotective effect highlights the potential therapeutic benefits of GLP-1RA in reducing secondary heart damage caused by CKD in the context of cardiorenal syndromes.