Amyloid beta-induced mitochondrial dysfunction and endothelial permeability in cerebral microvascular endothelial cells: The protective role of dexmedetomidine
Haifeng Zhao, Mingyue Fan, Jin Zhang, Yi Gao, Liang Chen, Lining Huang
Abstract
Postoperative cognitive dysfunction (POCD) is a common complication in patients who undergo anesthesia in different types of surgeries. Emerging evidence implicates elevated beta-amyloid (Aβ) in the pathogenesis of POCD. Meanwhile, Dexmedetomidine (DEX) has recently shown promise in reducing POCD incidence. This study aimed to elucidate the role of Aβ in inducing endothelial permeability in cerebral microvascular endothelial cells and the underlying mechanisms and testing the effects of DEX. We demonstrated that Aβ 1–42 , the prevalent Aβ form related to POCD, is cytotoxic to HBMECs, increasing transendothelial permeability and inducing mitochondrial dysfunction, as evidenced by elevated mitochondrial reactive oxygen species (ROS) and decreased ATP production and mitochondrial membrane potential. Furthermore, Aβ 1–42 was shown to inhibit Sirt3, exacerbating mitochondrial dysfunction. Conversely, DEX was found to prevent Aβ 1–42 -induced mitochondrial dysfunction and permeability increases and preserved tight junction proteins in HBMECs.These findings suggest that DEX, as a Sirt3 activator, may offer a pharmacological strategy to mitigate Aβ 1–42 -related cerebral microvascular endothelial cell dysfunction and preserve cognitive function post-surgery. • Aβ 1–42 inhibits Sirt3 expression and activity, worsening mitochondrial dysfunction in HBMECs. • Dexmedetomidine treatment inhibits Aβ 1–42 -induced mitochondrial dysfunction in HBMECs. • Sirt3 mediates Dexmedetomidine-prevented permeability increases in HBMECs.