Coronary Endothelium No‐Reflow Injury Is Associated with ROS‐Modified Mitochondrial Fission through the JNK‐Drp1 Signaling Pathway

Abstract

Coronary artery no-reflow is a complex problem in the area of reperfusion therapy, and the molecular mechanisms underlying coronary artery no-reflow injury have not been fully elucidated. In the present study, we explored whether oxidative stress caused damage to coronary endothelial cells by inducing mitochondrial fission and activating the JNK pathway. The hypoxia/reoxygenation (H/R) model was induced in vitro to mimic coronary endothelial no-reflow injury, and mitochondrial fission, mitochondrial function, and endothelial cell viability were analyzed using western blotting, quantitative polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Our data indicated that reactive oxygen species (ROS) were significantly induced upon H/R injury, and this was followed by decreased endothelial cell viability. Mitochondrial fission was induced and mitochondrial bioenergetics were impaired in cardiac endothelial cells after H/R injury. Neutralization of ROS reduced mitochondrial fission and protected mitochondrial function against H/R injury. Our results also demonstrated that ROS stimulated mitochondrial fission via JNK-mediated Drp1 phosphorylation. These findings indicate that the ROS-JNK-Drp1 signaling pathway may be one of the molecular mechanisms underlying endothelial cell damage during H/R injury. Novel treatments for coronary no-reflow injury may involve targeting mitochondrial fission and the JNK-Drp1 signaling pathway.

Propofol via Antioxidant Property Attenuated Hypoxia-Mediated Mitochondrial Dynamic Imbalance and Malfunction in Primary Rat Hippocampal Neurons

“…It was believed that in hippocampal neurons, phosphorylation of Drp1 at serine 616 (p-Drp1 ser 616 ) is positively correlated with mitochondrial fission while phosphorylation of Drp1 at serine 637 (p-Drp1 ser 637 ) is negatively correlated with mitochondrial fission [ 38 ]. We, together with other groups [ 39 ], proved hypoxia significantly increased p-Drp1 ser 616 ( Figure 7(b) ), while decreased p-Drp1 ser 637 ( Figure 7(d) ). In addition, we testified that p-Drp1 ser 616 was mediated through ERK ( Figure 7(a) ), while p-Drp1 ser 637 was mediated through PKA ( Figure 7(c) ).…”

Empagliflozin attenuates cardiac microvascular ischemia/reperfusion through activating the AMPKα1/ULK1/FUNDC1/mitophagy pathway

“…Mitophagy is regarded as an important repair mechanism for damaged and dysfunctional mitochondria through normalization of mitochondrial fission/fusion [ 59 ]. Increased mitochondrial fission and/or decreased mitochondrial fusion promotes the formation of fragmented mitochondria which promotes cellular oxidative stress or release pro-apoptotic factors (such as cytochrome c) into the cytoplasm where the mitochondria-dependent apoptosis is induced [ 9 , [60] , [61] , [62] ]. Mitophagy promotes the removal of fragmented mitochondria and therefore play anti-oxidative and/or anti-apoptotic roles in endothelial cells [ 11 , 63 ].…”

MELD-XI score predict no-reflow phenomenon and short-term mortality in patient with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

“…Endothelial dysfunction may be caused by the ROS produced by oxidative stress [ 17 ]. Previous studies have illustrated that endothelial cell damage caused by excessive oxidative stress has a strong association with NRP in patients with STEMI [ 18 – 20 ]. Celik et al [ 4 ] examined the associations between TB levels and NRP and in-hospital MACEs.…”