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Updated: Dec 13, 2025

Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Receptor for Advanced Glycation End Products is Involved in Platelet Hyperactivation and Arterial Thrombosis during
Jérémy Ortillon1, Nathalie Hézard2, Karim Belmokhtar1
1UMR CNRS 7369 Matrice Extracellulaire et Dynamique Cellulaire (MEDyC), Team 2 "Matrix Aging and Vascular Remodelling," Université de Reims Champagne Ardenne, Reims, France.
Background:
Chronic kidney disease (CKD) is associated with a high cardiovascular mortality due to increased rates of vascular lesions and thrombotic events, as well as serum accumulation of uremic toxins. A subgroup of these toxins (advanced glycation end products [AGEs] and S100 proteins) can interact with the receptor for AGEs (RAGE). In this study, we analyzed the impact of CKD on platelet function and arterial thrombosis, and the potential role of RAGE in this process.
Methods:
Twelve weeks after induction of CKD in mice, platelet function and time to complete carotid artery occlusion were analyzed in four groups of animals (sham-operated, CKD, apolipoprotein E [Apoe]-/-, and Apoe-/-/Ager-/- mice).
Results:
Analysis of platelet function from whole blood and platelet-rich plasma showed hyperactivation of platelets only in CKD Apoe-/- mice. There was no difference when experiments were done on washed platelets. However, preincubation of such platelets with AGEs or S100 proteins induced RAGE-mediated platelet hyperactivation. In vivo, CKD significantly reduced carotid occlusion times of Apoe-/- mice (9.2 ± 1.1 vs. 11.1 ± 0.6 minutes for sham, p < 0.01). In contrast, CKD had no effect on occlusion times in Apoe-/-/Ager-/- mice. Moreover, carotid occlusion in Apoe-/- CKD mice occurred significantly faster than in Apoe-/-/Ager-/- CKD mice (p < 0.0001).
Conclusion:
Our results show that CKD induces platelet hyperactivation, accelerates thrombus formation in a murine model of arterial thrombosis, and that RAGE deletion has a protective role. We propose that RAGE ligands binding to RAGE is involved in CKD-induced arterial thrombosis.
Insights
Chronic kidney disease (CKD) accelerates arterial thrombosis by causing platelet hyperactivation. Blocking the receptor for AGEs (RAGE) protects against this effect, suggesting RAGE is key in CKD-related vascular events.
Area of Science:
- Cardiovascular Science
- Nephrology
- Thrombosis Research
Background:
- Chronic kidney disease (CKD) is linked to high cardiovascular mortality, partly due to vascular lesions and thrombotic events.
- Uremic toxins, such as advanced glycation end products (AGEs) and S100 proteins, accumulate in CKD and can activate the receptor for AGEs (RAGE).
Purpose of the Study:
- To investigate the impact of CKD on platelet function and arterial thrombosis.
- To explore the role of the RAGE pathway in CKD-associated thrombotic complications.
Main Methods:
- Murine model of CKD was established 12 weeks prior to analysis.
- Platelet function and carotid artery occlusion times were assessed in sham-operated, CKD, apolipoprotein E knockout (Apoe-/-), and RAGE/Apoe double knockout (Apoe-/-/Ager-/-) mice.
Main Results:
- CKD induced platelet hyperactivation in Apoe-/- mice, but not in washed platelets, suggesting a role for plasma factors.
- Preincubation with AGEs or S100 proteins led to RAGE-mediated platelet hyperactivation.
- CKD significantly shortened carotid artery occlusion times in Apoe-/- mice, an effect abolished in Apoe-/-/Ager-/- mice.
Conclusions:
- CKD promotes platelet hyperactivation and accelerates arterial thrombus formation in a murine model.
- Deletion of RAGE confers a protective effect against CKD-induced arterial thrombosis.
- RAGE ligands binding to RAGE are implicated in the pathogenesis of CKD-associated arterial thrombosis.
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