Abstract: FR-PO0171
Plasmalemma Vesicle-Associated Protein Upregulation via VEGF-p38 MAPK Signaling Drives Aberrant Angiogenesis in Diabetic Cardiorenal Disease
Session Information
- Diabetic Kidney Disease: Metabolic, Mitochondrial, and Inflammatory Mechanisms
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Cardiovascular-Kidney-Metabolic Health
- 601 Cardiovascular-Kidney-Metabolic Health: Basic
Authors
- Wu, Jinshan, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Du, Xiaogang, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Lai, Han, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
Background
Diabetic cardiorenal disease is a major public health challenge worldwide. Endothelial dysfunction is a central driver of diabetic cardiorenal disease, however, the underlying molecular mechanisms remain incompletely understood. Our previous work identified Plasmalemma Vesicle Associated Protein (PLVAP) as a potential regulator of endothelial function in diabetic kidney disease, yet its specific roles in kidney and heart have not been fully elucidated.
Methods
Endothelial-specific Plvap knockout mice were generated and diabetes was induced using streptozotocin (STZ). The p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB202190 was used to assess signaling mechanisms. Mendelian randomization analysis was performed to exam the potential causal relationship between circulating PLVAP levels and cardiovascular nuclear magnetic resonance imaging (MRI) traits. In vitro, PLVAP was overexpressed or silenced in Human umbilical vein endothelial cells (HUVECs) and endothelial neoangiogenesis was assessed using tube formation assays.
Results
PLVAP expression was markedly increased in the glomeruli of human diabetic kidneys and was inversely correlated with renal function. Circulating PLVAP levels were also associated with cardiac function in humans. In HUVECs, PLVAP expression was upregulated by vascular endothelial growth factor (VEGF) and high glucose through activation of the p38-MAPK pathway. PLVAP overexpression significantly enhanced endothelial neoangiogenesis, an effect that was abolished by p38 inhibitor. In vivo, endothelial-specific deletion of PLVAP attenuated kidney injury and cardiac dysfunction.
Conclusion
PLVAP promotes the progression of diabetic cardiorenal disease by aggravating endothelial neoangiogenesis and dysfunction. Targeting PLVAP may therefore represent a promising therapeutic strategy for diabetic cardiorenal disease.
Funding
- Government Support – Non-U.S.