Abstract: FR-PO166
CD146 Deletion Protects against Kidney and Heart Damage after AKI
Session Information
- AKI: Mechanisms
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Boutin, Louis, UMR_S 1155, Common and Rare Kidney Diseases, Tenon Hospital, Paris, France
- Figueroa, Stefanny M., UMR_S 1155, Common and Rare Kidney Diseases, Tenon Hospital, Paris, France
- Hadjadj, Safia, UMR_S 1155, Common and Rare Kidney Diseases, Tenon Hospital, Paris, France
- Amar, Mouhamed, UMR_S 1155, Common and Rare Kidney Diseases, Tenon Hospital, Paris, France
- Roger, Elena, UMR_S 1155, Common and Rare Kidney Diseases, Tenon Hospital, Paris, France
- Elganfoud, Nadia, UMR-942, MASCOT, Cardiovascular Markers in Stress Condition, University Paris Cité, Paris, France
- Blot-Chabaud, Marcel, Aix-Marseille Univ, INSERM INRA, C2VN, Marseille, France
- Depret, François, UMR-942, MASCOT, Cardiovascular Markers in Stress Condition, University Paris Cité, Paris, France
- Samuel, Jane Lise, UMR-942, MASCOT, Cardiovascular Markers in Stress Condition, University Paris Cité, Paris, France
- Azibani, Feriel, UMR-942, MASCOT, Cardiovascular Markers in Stress Condition, University Paris Cité, Paris, France
- Chadjichristos, Christos E., UMR_S 1155, Common and Rare Kidney Diseases, Tenon Hospital, Paris, France
Background
AKI is linked to a higher risk of mortality and has been shown to increase heart failure, in months or years following the injury. CD146, an adhesion molecule mainly expressed in vascular endothelial cells, is elevated in patients with both renal and heart diseases. Recent findings show that CD146 increased expression within renal damaged endothelium exacerbates kidney inflammation and promotes tissue fibrosis in experimental nephropathy. Furthermore, mechanisms underlying AKI-induced cardiovascular damage remain poorly understood, including the role of CD146 in this process. Thus, this study assessed the role of CD146 in the progression of renal-cardio damage after renal ischemia-reperfusion (rIR).
Methods
Wild type (WT) and CD146 knock-out (KO) (2-3m) male mice, underwent a unilateral rIR of the left kidney after nephrectomy, with 25min of ischemia followed by 24h, 48h, and 28d of reperfusion. Sham group was submitted to a procedure without nephrectomy and rIR. Renal function was assessed by measuring creatininemia. Histological damage was evaluated by PAS or Sirius Red. Echocardiography was used to analyze heart function, and proinflammatory cytokines were studied by qPCR.
Results
CD146 was highly increased within renal endothelium at 24h (P<0.05) and 48h (P<0.01) in WT mice after rIR, and in the heart at 28d (P<0.05). As expected, after rIR renal function was temporarily altered as shown by plasma creatinine, increased at 24h (24.3±4.7 vs. 10.1±0.6µM in Sham), and 48h (20.0±3.1 vs. 6.3±0.4µM in Sham) and decreased over time. Interestingly, this increase was not observed in KO mice. In accordance, PAS showed preserved renal damage at 48h in KO mice compared to WT (P<0.05). In addition, increased expression of mRNA for proinflammatory cytokines, such as CCL2 and IL-1β, after 24 and 48h of rIR within damaged kidneys, and CCL2 in the heart at 28d, was blunted in KO (P<0.05). Furthermore, collagen deposition at 28d post-rIR in both kidney and heart was prevented in KO compared to WT mice (0.6 and 0.5 times, respectively). Finally, the absence of CD146 prevented the reduction in fractional shortening caused by rIR at 28d (46% in WT vs. 65% in KO mice).
Conclusion
Our results suggest that CD146 deletion protects against AKI and further heart damage after rIR in mice.
Funding
- Government Support – Non-U.S.