HIF-1介导的自噬在慢性肾脏病血管钙化中的研究进展

Research progress of HIF-1-mediated autophagy in vascular calcification in chronic kidney disease

血管钙化是慢性肾脏病患者的主要心血管风险因素,会增加慢性肾脏病患者的全因致死率。对于慢性肾脏病患者,长期的矿物质代谢紊乱、信号通路异常激活、激素水平改变及表观调控遗传异常基因表达等因素均会加速血管钙化。而血管平滑肌细胞的表型转换在血管钙化过程中发挥关键作用。自噬作为一种普遍存在的细胞内分解代谢过程,已被证实与血管平滑肌细胞的表型转换、凋亡有密切联系。低氧诱导因子-1(HIF-1)作为机体重要的转录因子,在低氧状态下可被上调并诱导下游靶基因BNIP3蛋白增加,促进自噬小体形成,从而改善心肌缺血的损伤程度,增强心肌保护。HIF-1介导的自噬可能是慢性肾脏病血管钙化的药物干预和治疗的新型靶点。

Vascular calcification is the major cardiovascular risk factor for chronic kidney disease,which will increase all-cause mortality in patients with chronic kidney disease.For patients with chronic kidney disease,long-term mineral metabolism disorders,abnormal activation of signaling pathways,changes in hormone levels and epigenetic abnormal gene expression will accelerate vascular calcification.Phenotypic transformation of vascular smooth muscle cells plays a key role in the vascular calcification.Autophagy,as a ubiquitous intracellular catabolic process,has been proved to be closely related to phenotypic transformation and apoptosis of vascular smooth muscle cells.Hypoxia-inducible factor-1(HIF-1)as an important transcription factor in the body,which induces the increase in the downstream target gene BNIP3 protein after being up-regulated under hypoxia,promoting the formation of autophagosomes,thereby improving the degree of myocardial ischemia injury and enhancing myocardial protection.Therefore,HIF-1-mediated autophagy may be a new target for drug intervention and treatment of vascular calcification in chronic kidney disease.