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

GSE308324 Mus musculus Expression profiling by high throughput sequencing 6 samples Submitted 2025/09/17 Platform GPL24247
Summary
This study investigates the molecular mechanisms by which L-proline contributes to diabetic heart failure with preserved ejection fraction (HFpEF) through the induction of ferroptotic stress under metabolic conditions. We found that L-proline exacerbates ferroptosis-related oxidative and lipid peroxidation stress in cardiac tissue within a metabolically driven HFpEF context. Mechanistically, L-proline markedly suppressed PPARγ signaling, a key regulator of lipid metabolism, redox homeostasis, and ferroptosis resistance. Downregulation of PPARγ was accompanied by upregulation of pro-ferroptotic mediators, including ACSL4 and TFR1, indicating enhanced iron-dependent lipid peroxidation and ferroptotic susceptibility. These findings support a mechanistic link between amino acid metabolic remodeling and fibroblast-centered cardiac vulnerability in diabetic HFpEF, highlighting the role of the proline–PPARγ–ferroptosis axis in promoting myocardial fibrosis and diastolic dysfunction under chronic metabolic stress.
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Also filed as BioProject PRJNA1330196 and SRA study SRP621122. Searching any of these in the dataset finder brings you back here.

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