Remote ischemic preconditioning reduces myocardial ischemia–reperfusion injury through unacylated ghrelin-induced activation of the JAK/STAT pathway

Sawashita, Yasuaki; Hirata, Naoyuki; Yoshikawa, Yusuke; Terada, Hirofumi; Tokinaga, Yasuyuki; Yamakage, Michiaki

doi:10.1007/s00395-020-0809-z

Cited by 45 publications

(40 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although there has been an advancement in drugs and interventional therapies in recent years, breakthrough progress has not been achieved in the prevention and treatment of coronary no-reflow injury following reperfusion therapy [2,49]. Since infarction size, cardiac remodeling, myocardial function, and all-cause death are also determined by coronary no-reflow injury; understanding the molecular mechanisms underlying coronary no-reflow will promote specific diagnoses and therapies in clinical practice [11,50]. In the present study, we used an H/R injury model to mimic coronary artery no-reflow injury in vitro.…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Liu

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Chen

Liu

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

show abstract

“…For the invasion assay, the upper chamber was treated with Matrigel before cells were added. After incubation for 48 h, cells that had migrated to or invaded the lower chamber were stained with 0.1% crystal violet and quantified using a microscope [53].…”

Section: Mitochondrial Membrane Potential (Mmp) Assessmentmentioning

confidence: 99%

Melatonin Attenuates ox‐LDL‐Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

Xie¹,

Zhong

Guo

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Endothelial dysfunction, which is characterized by damage to the endoplasmic reticulum (ER) and mitochondria, is involved in a variety of cardiovascular disorders. Here, we explored whether mitochondrial damage and ER stress are associated with endothelial dysfunction. We also examined whether and how melatonin protects against oxidized low-density lipoprotein- (ox-LDL-) induced damage in endothelial cells. We found that CHOP, GRP78, and PERK expressions, which are indicative of ER stress, increased significantly in response to ox-LDL treatment. ox-LDL also induced mitochondrial dysfunction as evidenced by decreased mitochondrial membrane potential, increased mitochondrial ROS levels, and downregulation of mitochondrial protective factors. In addition, ox-LDL inhibited antioxidative processes, as evidenced by decreased antioxidative enzyme activity and reduced Nrf2/HO-1 expression. Melatonin clearly reduced ER stress and promoted mitochondrial function and antioxidative processes in the presence of ox-LDL. Molecular investigation revealed that ox-LDL activated the JNK/Mff signaling pathway, and melatonin blocked this effect. These results demonstrate that ox-LDL induces ER stress and mitochondrial dysfunction and activates the JNK/Mff signaling pathway, thereby contributing to endothelial dysfunction. Moreover, melatonin inhibited JNK/Mff signaling and sustained ER homeostasis and mitochondrial function, thereby protecting endothelial cells against ox-LDL-induced damage.

show abstract

“…After exposure to each condition for 6 h, myocardial ischemia-reperfusion injury was induced in all rats using the methods of Sawashita et al [ 19 ]. Briefly, after rats were anesthetized intraperitoneally using a mixture of anesthetic agents (midazolam, 2 mg/kg; butorphanol, 2.5 mg/kg; and medetomidine, 0.15 mg/kg), the trachea was intubated with a 16-gauge cannula and the rat was mechanically ventilated using a volume-controlled mode with the tidal volume set to 1 mL/100 g body weight at a respiratory rate of 60 breaths/min (model 683 Small Animal Ventilator; Harvard Apparatus, Holliston, MA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The LAD was then reoccluded and 4% Evans blue was injected to determine the “area at risk” (AAR) as previously described [ 19 , 20 ]. The heart was excised under deep anesthesia, the LV was sliced at thickness of 2 mm and these slices were incubated in a 1% solution of 2,3,5-triphenyltetrazolium chloride dye for 15 min at 37°C and then fixed in 10% formalin for 20 min.…”

Section: Methodsmentioning

confidence: 99%

Acute Hypobaric and Hypoxic Preconditioning Reduces Myocardial Ischemia-Reperfusion Injury in Rats

Terada

Hirata

Sawashita

et al. 2021

Cardiology Research and Practice

Self Cite

View full text Add to dashboard Cite

Background. Chronic and/or intermittent exposure to hypobaric hypoxia reportedly exerts cardioprotective effects against ischemia-reperfusion injury. However, few studies have focused on the cardioprotective effects of acute and/or short-term hypobaric and hypoxic exposures. This study investigated the effects of acute hypobaric hypoxia on myocardial ischemia-reperfusion injury. Materials and Methods. Rats were assigned to groups receiving normobaric normoxia (NN group), hypobaric hypoxia (HH group), or normobaric hypoxia (NH group). HH group rats were exposed to 60.8 kPa and 12.6% fraction of inspired oxygen in a hypobaric chamber for 6 h. NH group rats were exposed to hypoxic conditions under normal pressure. After each exposure, 30 min of myocardial ischemia was followed by 60 min of reperfusion. Cardiac function and infarct size were determined after reperfusion. Expression of hypoxia-inducible factor 1 alpha (HIF1α) was also measured. Results. Cardiac function was better preserved in the HH and NH groups than in the NN group ( p < 0.01 each). Median infarct size/area at risk was significantly lower in the HH group (50%, interquartile range [IQR] 48–54%; p < 0.01 vs. NN group) and NH group (45%, IQR 36–50%; p < 0.01 vs. NN group) than in the NN group (72%, IQR 69–75%). HIF1α expression was significantly higher in the HH group ( p < 0.05 vs. NN group) and NH group ( p < 0.01 vs. NN group) than in the NN group. Conclusions. Exposure to acute and/or short-term hypobaric and hypoxic conditions might exert cardioprotective effects against myocardial ischemia-reperfusion injury via HIF1α modulation.

show abstract

Remote ischemic preconditioning reduces myocardial ischemia–reperfusion injury through unacylated ghrelin-induced activation of the JAK/STAT pathway

Cited by 45 publications

References 91 publications

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

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

Melatonin Attenuates ox‐LDL‐Induced Endothelial Dysfunction by Reducing ER Stress and Inhibiting JNK/Mff Signaling

Acute Hypobaric and Hypoxic Preconditioning Reduces Myocardial Ischemia-Reperfusion Injury in Rats

Contact Info

Product

Resources

About