Abstract: TH-PO0272
Combined Effects of GLP-1 Receptor Agonist and SGLT2 Inhibitor on Inflammatory Modulation in Hypoxia-Induced Renal Tubular and Endothelial Cell Injury
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
- Oliveira, Julia Cristine, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
- de Jesus, Thais Silva, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
- Figueredo, Guilherme Rocha, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
- Brasil, Giulia Quinto, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
- Quinto, Beata M r, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
- Batista, Marcelo Costa, Universidade Federal de Sao Paulo, São Paulo, SP, Brazil
Group or Team Name
- LORDc - UNIFESP.
Background
Chronic low-grade inflammation in obesity plays a key role in kidney and cardiovascular disease. MicroRNAs regulate adipose–endothelial signaling, modulating inflammation, metabolism and insulin sensitivity. GLP-1 receptor agonists and SGLT2 inhibitors have shown reno- and cardioprotective effects, but their combined impact on hypoxia-induced inflammation and injury is poorly defined.
Methods
HK-2 and HUVECs were exposed to six conditions: control, hypoxia, hypoxia + inflammation (leptin + TGF-β), and inflammation plus liraglutide (GLP-1 RA), dapagliflozin (SGLT2i), or both. Cytokines (leptin, IL-6, TNF-α, IL-10, IL-1β), NGAL and KIM-1 were measured by multiplex immunoassay and HIF1α, ICAM, VCAM, TNF-α, and IL-10 expression, by immunofluorescence. ANOVA with Bonferroni correction was used (p < 0.05).
Results
The inflammatory model significantly elevated leptin, TNF-α, and IL-6 levels in both HK-2 and HUVECs (p < 0.05). HUVECs also demonstrated increased IL-10, NGAL and KIM-1. Co-treatment with liraglutide and dapagliflozin reduced proinflammatory cytokines and tubular injury markers in both cells, though not all changes achieved statistical significance. Immunofluorescence confirmed upregulation of HIF1α, ICAM, VCAM, TNF-α, and IL-10 in HK-2 cells under inflammatory conditions, which was attenuated by the combination therapy.
Conclusion
Hypoxia combined with leptin and TGF-β induces a robust proinflammatory and injurious response in renal tubular and endothelial cells. Combined treatment with liraglutide and dapagliflozin effectively mitigates these effects, supporting a synergistic anti-inflammatory and renoprotective role. These findings provide mechanistic insight into the potential of dual GLP-1 RA and SGLT2i therapy for mitigating kidney injury in metabolic disease contexts.
Funding
- Government Support – Non-U.S.