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Characterization of renal anomalies in an experimental model of heart failure with preserved ejection fraction (HFpEF) in rats

par Sheikh Mohammad, Umair ;Hubesch, Geraldine ;Van Eycken, Marie ;Rorive, Sandrine ;Nortier, Joëlle ;El Fahsi, Bilal ;Vegh, Grégory ;Singh, Sumeet Pal ;Hupkens, Emeline ;Jespers, Pascale ;McEntee, Kathleen ;Vachiery, Jean-Luc ;Dewachter, Céline ;Dewachter, Laurence
Référence Basic Science Research in Cardiology (07-12-2023: Ku Leuven, Leuven, Belgium)
Publication Publié, 2023-12-07

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Résumé :

Heart failure with preserved ejection fraction (HFpEF) is a global cardiovascular challenge, constituting nearly 50% of prevalent heart failure cases worldwide. Renal dysfunction is common in HFpEF and is linked to higher mortality. The interplay between HFpEF and chronic kidney disease, potentially through a bidirectional causative relationship, remains poorly understood. In our study, we explored renal abnormalities over time in an experimental rat model of HFpEF with multiple comorbidities. Obesity-prone (OP) and–resistant (OR) rats were fed a high fat diet (HFD) or a standard rat chow for 4 or 12 months (n= 10 rats/group). They underwent evaluation through echocardiography, cardiac catheterization, and renal histological analyses. After 12 months of HFD, OP rats developed HFpEF, featuring LV diastolic dysfunction, concentric LV hypertrophy, and fibrosis, while maintaining preserved LV ejection fraction—absent in the 4-month HFD group. HFpEF rats exhibited increased serum cystatin C levels and elevated renal expression of kidney injury molecule (KIM)-1, indicating renal dysfunction. Histological analysis revealed glomerular enlargement, sclerosis, and inflammatory infiltrates in 4-month HFD fed OP rats, intensified in HFpEF rats. Increased renal expression of inflammatory markers, adhesion molecules, and macrophage-specific marker CD68 was observed. Pro-inflammatory cytokines and indicators of renal apoptosis and sustained fibrosis were heightened in HFpEF rats, demonstrating matrix component upregulation and increased expression of pro-fibrotic factors. Our findings showed renal pathological alterations preceding HFpEF diagnosis in our experimental rat model, pointing out the intricate relationship between HFpEF and renal dysfunction.