Department of Cardiology, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.
Cardiovasc Diabetol. 2024 Nov 26;23(1):424. doi: 10.1186/s12933-024-02519-1.
Diabetic cardiomyopathy (DCM) is a severe cardiovascular complication of diabetes characterized by myocardial hypertrophy, fibrosis, and impaired cardiac function. Fibroblast growth factor 21 (FGF21) has emerged as a promising therapeutic target due to its antifibrotic, antioxidant, and anti-inflammatory properties. Our commentary summarizes and affirms the recent study by Wang et al., which demonstrates the significant role of ferroptosis in DCM pathogenesis. FGF21 has shown promise as a therapeutic target for DCM, potentially inhibiting ferroptosis, mitigating oxidative damage, and protecting cardiomyocyte function. Mechanistically, the study identified ATF4 as an upstream regulator of FGF21 in DCM, revealing that FGF21 directly interacts with ferritin and extends its half-life, thus inhibiting ferroptosis in DCM. These findings provide a theoretical basis for understanding the pathogenesis and treatment of DCM. Our commentary suggests that future studies should explore the role of non-cardiomyocyte cell types in DCM, verify findings with clinical samples, and address comprehensive methods for ferroptosis detection. Additionally, we discuss the clinical application and future potential of FGF21-based therapies for DCM. Such efforts may contribute to advancing DCM diagnosis and treatment, fostering the development of innovative therapeutic strategies.
糖尿病心肌病（DCM）是糖尿病的一种严重心血管并发症，其特征为心肌肥大、纤维化和心脏功能受损。成纤维细胞生长因子 21（FGF21）因其具有抗纤维化、抗氧化和抗炎特性而成为有前途的治疗靶点。我们的评论总结并肯定了 Wang 等人最近的研究，该研究表明铁死亡在 DCM 发病机制中的重要作用。FGF21 作为 DCM 的治疗靶点具有潜力，可能抑制铁死亡、减轻氧化损伤并保护心肌细胞功能。在机制上，该研究确定了 ATF4 是 DCM 中 FGF21 的上游调节剂，表明 FGF21 直接与铁蛋白相互作用并延长其半衰期，从而抑制 DCM 中的铁死亡。这些发现为理解 DCM 的发病机制和治疗提供了理论基础。我们的评论还建议，未来的研究应该探讨非心肌细胞类型在 DCM 中的作用，用临床样本验证研究结果，并采用综合方法检测铁死亡。此外，我们还讨论了基于 FGF21 的治疗方法在 DCM 中的临床应用和未来潜力。这些努力可能有助于推进 DCM 的诊断和治疗，促进创新治疗策略的发展。
