Role of Autophagy in Endothelial Damage and Blood–Brain Barrier Disruption in Ischemic Stroke
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The global burden of neurological diseases including stroke has significantly increased,1 and an urgent need exists to develop new treatment strategies. Impairment of autophagic regulation has been observed in diseases including neurodegenerative diseases and ischemic stroke, suggesting that modulation of autophagy could be a potential therapeutic target.2 Endothelial cells (ECs) maintain homeostasis by regulating the vascular tone and permeability and endothelial dysfunction is associated with diverse cardiovascular diseases (CVDs). The integrity of the blood–brain barrier (BBB), which shows selective permeability for substances into the brain, is significantly impaired under ischemic stroke. This review focuses on autophagy in endothelial dysfunction in the context of ischemic stroke and potential targets for therapeutic manipulation.
Physiological Roles and Clinical Importance of Autophagy
Autophagy or autophagocytosis is an evolutionarily conserved mechanism for the degradation and recycling of cellular organelles and protein.2 It occurs continually at basal levels in cells and contributes to the maintenance of cellular homeostasis. When external nutrient supplies are limited, cells attempt to generate their energy by degrading and recycling macromolecules and cellular organelles by autophagy.3
Autophagy is also an important defense mechanism against stress including oxidative stress and infection, enabling cellular repair, or clearance of pathogens.1,2 Defects in autophagy flux may lead to the accumulation of damaged or senescent proteins and abnormal protein aggregates, and this is closely associated with human diseases including neurodegenerative, cardiovascular, and metabolic diseases, as well as cancer.2,4 In contrast to the protective role of autophagy in maintaining basal cellular homeostasis, excessive autophagy may also cause dysregulation of catabolic activity and maladaptation to cellular stress, leading to autophagic cell death.5
Accumulating evidence shows that modulating the level of autophagy by targeting specific regulatory molecules in the autophagy machinery may impact disease onset or disease …