铁死亡与冠心病的临床研究进展

Clinical Research Progress on Ferroptosis in Coronary Heart Disease

摘要: 冠心病(CHD)是一种严重的心血管疾病，发病机制复杂多样，铁死亡是一种近年来被广泛研究的铁依赖性程序性细胞死亡方式。本综述综合了当前关于CHD铁死亡机制和新兴临床干预策略的研究。铁死亡的特征是铁代谢失调、脂质过氧化和活性氧(ROS)积累，这些过程与CHD病理生理学密切相关。在缺血和缺氧条件下，心肌细胞易受铁死亡的影响，导致心肌细胞功能障碍和心脏功能下降。有研究表明，铁代谢相关蛋白(包括GPX4、FTH1、TfR1和HO-1)表达的改变、脂质过氧化产物的积累以及抗氧化防御系统(尤其是Nrf2/GPX4通路)的破坏是心脏组织铁死亡进展的核心。在临床上，特异性铁死亡抑制剂(如Ferrostatin-1)已成为有前景的候选治疗药物。然而，对CHD铁死亡机制的研究尚处于早期阶段，关于其与其他细胞死亡途径的关系以及铁死亡靶向干预的临床治疗方案有待进一步研究。未来的研究方向应包括更多深入机制的研究及对心血管疾病中铁死亡途径更有效、更安全的临床干预措施的开发。

Abstract: Coronary heart disease (CHD) is a serious cardiovascular condition with complex and diverse pathogenic mechanisms. Ferroptosis, an iron-dependent form of regulated cell death, has been extensively studied in recent years. This review synthesizes current research on ferroptosis mechanisms in CHD and emerging clinical intervention strategies. Characterized by dysregulated iron metabolism, lipid peroxidation, and reactive oxygen species (ROS) accumulation, ferroptosis processes are closely linked to CHD pathophysiology. Under ischemic and hypoxic conditions, cardiomyocytes become particularly vulnerable to ferroptosis, leading to myocardial dysfunction and cardiac performance deterioration. Studies demonstrate that altered expression of iron metabolism-related proteins (including GPX4, FTH1, TfR1, and HO-1), accumulation of lipid peroxidation products, and impairment of the antioxidant defense system (particularly the Nrf2/GPX4 pathway) constitute the core mechanisms driving ferroptosis progression in cardiac tissue. Clinically, specific ferroptosis inhibitors (e.g., Ferrostatin-1) have emerged as promising therapeutic candidates. However, research on ferroptosis mechanisms in CHD remains in its early stages, with further investigation needed regarding its interplay with other cell death pathways and the development of targeted clinical interventions. Future research directions should include more in-depth mechanistic studies and the development of safer, more effective clinical approaches targeting ferroptosis pathways in cardiovascular diseases.