鱼藤酮对血管内皮细胞自噬与凋亡的双向调控机制研究进展OA

Vascular endothelial cell(VEC)homeostasis is essential to the preservation of the struc-tural and functional integrity of vessels,whereas endothelial dysfunction acts as a core early trigger of diverse cardiovascular diseases(CVDs).The synergistic regulation of oxidative stress,autophagy and apoptosis determines the fate of VECs under both physiological and pathological conditions.As a classic inhibitor of mitochondrial complex Ⅰ,rotenone interrupts mitochondrial electron transport and triggers excessive reactive oxygen species(ROS)buildup,which disrupts cellular redox balance and energy metabolism,and consequently compromises multiple biological functions of VECs.Recent studies suggest that rotenone exerts bidirectional regulatory effects on VECs in that low levels of rotenone can suppress oxidative stress,restore endothelial activity and offer vascular protection,thereby retarding atherosclerotic progression.Conversely,high-dose rotenone exposure exacerbates oxidative damage,disturbs autophagic flux,induces endothelial apoptosis,and ultimately impairs the integrity of the vascular endothelial barrier.The rotenone-triggered alterations in oxidative status,autophagic activity and apop-totic progression are not restricted to VECs,but commonly occur in various cell types,indicating the generalizability of such cellular responses.Even so,the unique microenvironmental and functional features of VECs may modulate their sensitivity and responsive patterns upon rotenone stimulation.This review summarizes the biological properties and molecular mechanisms of rotenone,as well as its molecular network regulating autophagy and apoptosis in VECs.The conserved cellular mechanisms of rotenone bioactivity and its potential tissue-specific regulatory characteristics are also analyzed,alongside its pathological significance in the development of CVDs.This study is expected to shed light on the mechanisms of rotenone-induced cardiotoxicity and related prevention and treatment strategies.