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自噬在心血管疾病中的研究进展
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Abstract:
自噬作为真核细胞清除受损成分、维持稳态的关键机制，通过巨自噬、微自噬和分子伴侣介导自噬三种形式动态调控细胞命运。自噬活性受mTOR、AMPK及Mst1等信号通路精密调控。在心血管疾病中，自噬呈现双向作用：心力衰竭早期适度自噬通过清除受损线粒体延缓心衰进展，但过度激活会破坏自噬流稳态，加剧病理性重塑；心肌缺血阶段自噬发挥保护作用，而再灌注期ROS诱导的异常自噬则加重细胞死亡；糖尿病心肌病中自噬活性随病程呈现动态变化，早期抑制自噬可缓解纤维化，长期增强自噬以改善线粒体功能；阿霉素心肌损伤中自噬兼具保护与毒性双重角色。当前研究强调自噬通量动态平衡的重要性，但是自噬与铁死亡等非经典凋亡途径的交互作用将会给未来研究、治疗等提供新方向。
As a pivotal mechanism for eukaryotic cells to eliminate damaged components and maintain homeostasis, autophagy dynamically regulates cellular fate through three forms: macroautophagy, micro-autophagy, and chaperone-mediated autophagy. Autophagic activity is precisely regulated by signaling pathways including mTOR, AMPK, and Mst1. In cardiovascular diseases, autophagy exhibits dual roles: during early-stage heart failure, moderate autophagy delays disease progression by clearing damaged mitochondria, while excessive activation disrupts autophagic flux homeostasis and exacerbates pathological remodeling. Myocardial ischemia benefits from protective autophagy, whereas reperfusion-induced ROS triggers aberrant autophagy that aggravates cell death. Diabetic cardiomyopathy demonstrates dynamic changes in autophagic activity throughout disease progression—early-stage autophagy inhibition alleviates fibrosis, while long-term enhancement improves mitochondrial function. In doxorubicin-induced cardiotoxicity, autophagy manifests both protective and toxic effects. Current research emphasizes the importance of autophagy flux homeostasis, but the interaction between autophagy and ferroptosis and other non-canonical apoptotic pathways will provide new directions for future research and treatment.
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