Background: Inflammation is central to acute kidney injury (AKI) and its systemic consequences. AKI triggers endothelial dysfunction that predisposes patients to long-term cardiovascular complications and increase mortality. CD146, an adhesion molecule upregulated in both renal and cardiac disorders, promotes kidney inflammation and fibrosis. However, its role in connecting the renal ischemia–reperfusion (rIR) to subsequent cardiac injury remains unclear. This study investigated the role of CD146 in renal and cardiac inflammation after rIR. Methods: Wild-type (WT) males and CD146 knockout (KO) mice (8–12 weeks) underwent left unilateral rIR after contralateral nephrectomy (25 minutes of ischemia; 24, 48 hours (h), or 28 days (d) of reperfusion) (n=5-7). Sham animals underwent surgery without nephrectomy or ischemia (n=3-5). Renal function was assessed by measuring plasma creatinine and urea. Renal and cardiac injury were evaluated using Periodic acid–Schiff (PAS), Sirius Red or immunohistochemistry. Cardiac function assessed using fractional shortening analysed by M-mode echocardiography. Pro-inflammatory cytokines were quantified by RT-qPCR. Values are expressed in mean±SEM (standard error of the mean). Results: In WT mice, CD146 expression increased markedly in the renal endothelium at 24h (p< 0.05) and 48h (p< 0.01) post-rIR, and in the heart at 28d (p< 0.05). rIR caused an acute rise in plasma creatinine at 24h (24.3±4.7 vs. 10.1±0.6 µmol/L in Sham) and 48h (20.0±3.1 vs. 6.3±0.4 µmol/L in Sham), followed by partial recovery—changes not observed in KO mice. Consistently, PAS staining revealed preserved renal structure in KO mice at 48h, compared with the WT mice (p< 0.05). Induction of pro-inflammatory cytokines (CCL2, IL-1β) in the kidney at 24–48h and CCL2 in the heart at 28d was blunted in KO animals (p< 0.05). CD146 deletion also prevented monocyte/macrophage recruitment, evidenced by reduced IBA-1 immunostainings at 48h (p< 0.05), and abrogated the rIR-induced upregulation of macrophage polarization markers YM-1, CD163, and CD206 (p< 0.01). In addition, fibrosis at 28d was lower in KO mice, with reduced collagen deposition in both kidney and heart (0.63- and 0.45-fold vs. WT). Finally, CD146 deficiency preserved cardiac function, since the decline of fractional shortening observed in WT mice at 28 d was prevented (45.8% WT vs. 65.4% KO). Conclusion: CD146 mediates renal inflammation and drives secondary cardiac dysfunction after rIR. Genetic deletion of CD146 attenuates kidney inflammation, immune-cell recruitment, fibrosis, and long-term cardiac impairment. Acknowledgments: This work was supported by the French National Research Agency (ANR GalCAM-AKI grant, ANR-22-CE14-0045), the French National Institute of Health and Medical Research (Inserm) Sorbonne University and APHP (Paris public hospital). This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Figueroa et al. (Fri,) studied this question.