TY - JOUR
T1 - Preventing ischemia-reperfusion injury by acousto-mechanical local oxygen delivery
AU - Ho, Yi Ju
AU - Hsu, Hui Ching
AU - Wu, Bing Huan
AU - Lin, Yu Chun
AU - Liao, Lun De
AU - Yeh, Chih Kuang
N1 - Publisher Copyright:
© 2023
PY - 2023/4
Y1 - 2023/4
N2 - Ischemia-reperfusion (I/R) injury is a pathological process that causes vascular damage and dysfunction which increases recurrence and/or mortality in myocardial infarction, ischemic stroke, and organ transplantation. We hypothesized that ultrasound-stimulated oxygen-loaded microbubble (O2-MB) cavitation would enhance mechanical force on endothelium and simultaneously release oxygen locally at the targeted vessels. This cooperation between biomechanical and biochemical stimuli might modulate endothelial metabolism, providing a potential clinical approach to the prevention of I/R injury. Murine hindlimb and cardiac I/R models were used to demonstrate the feasibility of injury prevention by O2-MB cavitation. Increased mechanical force on endothelium induced eNOS-activated vasodilation and angiogenesis to prevent re-occlusion at the I/R vessels. Local oxygen therapy increased endothelial oxygenation that inhibited HIF-1α expression, increased ATP generation, and activated cyclin D1 for cell repair. Moreover, a decrease in interstitial H2O2 level reduced the expression of caspase3, NFκB, TNFα, and IL6, thus ameliorating inflammatory responses. O2-MB cavitation showed efficacy in maintaining cardiac function and preventing myocardial fibrosis after I/R. Finally, we present a potential pathway for the modulation of endothelial metabolism by O2-MB cavitation in relation to I/R injury, wound healing, and vascular bioeffects.
AB - Ischemia-reperfusion (I/R) injury is a pathological process that causes vascular damage and dysfunction which increases recurrence and/or mortality in myocardial infarction, ischemic stroke, and organ transplantation. We hypothesized that ultrasound-stimulated oxygen-loaded microbubble (O2-MB) cavitation would enhance mechanical force on endothelium and simultaneously release oxygen locally at the targeted vessels. This cooperation between biomechanical and biochemical stimuli might modulate endothelial metabolism, providing a potential clinical approach to the prevention of I/R injury. Murine hindlimb and cardiac I/R models were used to demonstrate the feasibility of injury prevention by O2-MB cavitation. Increased mechanical force on endothelium induced eNOS-activated vasodilation and angiogenesis to prevent re-occlusion at the I/R vessels. Local oxygen therapy increased endothelial oxygenation that inhibited HIF-1α expression, increased ATP generation, and activated cyclin D1 for cell repair. Moreover, a decrease in interstitial H2O2 level reduced the expression of caspase3, NFκB, TNFα, and IL6, thus ameliorating inflammatory responses. O2-MB cavitation showed efficacy in maintaining cardiac function and preventing myocardial fibrosis after I/R. Finally, we present a potential pathway for the modulation of endothelial metabolism by O2-MB cavitation in relation to I/R injury, wound healing, and vascular bioeffects.
KW - Ischemia-reperfusion injury
KW - Mechanical force
KW - Oxygen microbubble
KW - Oxygen therapy
KW - Ultrasound
UR - http://www.scopus.com/inward/record.url?scp=85150063052&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2023.03.018
DO - 10.1016/j.jconrel.2023.03.018
M3 - Article
C2 - 36921723
AN - SCOPUS:85150063052
SN - 0168-3659
VL - 356
SP - 481
EP - 492
JO - Journal of Controlled Release
JF - Journal of Controlled Release
ER -