Transcriptomic Profiling of L-Proline Induced Ferroptosis Reveals PPARγ-Mediated Regulatory Networks in HFpEF Progression

This study investigates the molecular mechanisms by which L-proline contributes to heart failure with preserved ejection fraction (HFpEF) through ferroptosis. L-proline was found to exacerbate ferroptotic stress in cardiac tissue, partly by modulating the expression of key antioxidant and lipid metabolism genes. Notably, L-proline suppressed PPARγ signaling, a critical regulator of ferroptosis resistance and metabolic homeostasis. Downregulation of PPARγ led to activation of pro-ferroptotic mediators, including ACSL4 and TFR1, suggesting a mechanistic link between amino acid metabolism and cardiac vulnerability in HFpEF. A murine HFpEF model was induced via high-fat diet and L-NAME. Mice were divided into control and L-proline treated groups. After 8 weeks, left ventricular tissue was harvested for total RNA extraction. Differentially expressed genes associated with L-proline–induced ferroptosis and PPARγ signaling were identified by RNA sequencing using Illumina NovaSeq 6000. Bioinformatic analysis included: