Maternal diabetes up‐regulates NOX2 and enhances myocardial ischaemia/reperfusion injury in adult offspring

Zhang, Lili; Wang, Xiaoyan; Wu, Yan; Lu, Xiangru; Chidiac, Peter; Wang, Guoping; Feng, Qingping

doi:10.1111/jcmm.13500

Cited by 13 publications

(12 citation statements)

References 45 publications

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“…In cardiomyocytes, ROS production is primarily regulated by Nox2 [ 27 ] and cleared by SOD [ 28 ]. Studies have reported that increasing the expression of Nox2 can enhance ROS production and ultimately enhance myocardial ischaemia-reperfusion injury, and this finding may be related to the activation of the AKT signal pathway [ 29 ]. In our experiments, after hypoxia-reoxygenation, the ROS content in cardiomyocytes increased; the increase positively correlated with the expression of Bax, Nox2, and the rate of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Released from CaSR‐Stimulated PMNs Reduce Ischaemia/Reperfusion Injury

Zhai

Cui

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ischemia-reperfusion (I/R) injury caused by acute myocardial infarction (AMI) can initiate a strong inflammatory response. Polymorphonuclear cells (PMNs) are the most important inflammatory cells. Our previous studies found that the calcium-sensing receptor (CaSR) regulates the proinflammatory effects of PMNs. However, the role and mechanism of CaSR-regulated PMNs in I/R injury remain uncertain. A rat AMI model was developed in this study and showed that the expression of CaSR on PMNs increased in AMI; however, the levels of Bcl-xl and SOD in myocardial tissue decreased, while Bax and MDA levels increased. Then, after coculture with CaSR-stimulated PMNs, the expression of Bcl-xl in cardiomyocytes significantly increased, Bax expression and the apoptotic rate decreased, and ROS production was significantly inhibited. At the same time, the cardiomyocyte damage caused by hypoxia-reoxygenation was reduced. Furthermore, we found that exosomes derived from PMNs could be taken up by cardiomyocytes. Additionally, the exosomes secreted by CaSR-stimulated PMNs had the same effect on cardiomyocytes as CaSR-stimulated PMNs, while the increased phosphorylation level of AKT in cardiomyocytes could be revered by AKT transduction pathway inhibitors. Subsequently, we identified the exosomes derived from CaSR-stimulated PMNs by second-generation sequencing technology, and increased expression of lncRNA ENSRNOT00000039868 was noted. The data show that this lncRNA can prevent the hypoxia-reoxygenation injury by upregulating the expression of PDGFD in cardiomyocytes. In vivo, exosomes from CaSR-stimulated PMNs played a significant role against AMI and reperfusion injury in myocardial tissue. Thus, we propose that exosomes derived from CaSR-stimulated PMNs can reduce I/R injury in AMI, and this effect may be related to the AKT signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Exosomes Released from CaSR‐Stimulated PMNs Reduce Ischaemia/Reperfusion Injury

Zhai

Cui

Zhou

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…Oxidative and inflammatory stresses are among the pathophysiological changes postulated to occur in response to I/R ( Aragno et al, 2003 ; Chen et al, 2007 ; Wong and Crack, 2008 ; Granger and Kvietys, 2015 ; Kurian et al, 2016 ; Rovcanin et al, 2016 ; Gao et al, 2017 ). Thus, we examined the expression of the following proteins involved in oxidative stress and inflammation: NOX2 ( Lou et al, 2018 ; Zhang et al, 2018 ), ORP150 ( Kitano et al, 2004 ; Ye et al, 2013 ), SOD1 ( Jiang et al, 2015 ; Dibas et al, 2018 ), SOD2 ( Haines et al, 2010 ; Xu et al, 2010 ), NLRP3 ( He et al, 2017 ; Liu et al, 2018 ), NF-κβ ( Su et al, 2017 ; Ye et al, 2017 , 2018 ), and IFNγ ( Sun et al, 2016 ; Ferhat et al, 2018 ). The high expression of these proteins in the present I/R model implied that even a short period of ischemia, followed by reperfusion, played a major role in exaggerating tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Chick Embryo: A Preclinical Model for Understanding Ischemia-Reperfusion Mechanism

et al. 2018

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Ischemia-reperfusion (I/R)-related disorders, such as stroke, myocardial infarction, and peripheral vascular disease, are among the most frequent causes of disease and death. Tissue injury or death may result from the initial ischemic insult, primarily determined by the magnitude and duration of the interruption in blood supply and then by the subsequent reperfusion-induced damage. Various in vitro and in vivo models are currently available to study I/R mechanism in the brain and other tissues. However, thus far, no in ovo I/R model has been reported for understanding the I/R mechanisms and for faster drug screening. Here, we developed an in ovo Hook model of I/R by occluding and releasing the right vitelline artery of a chick embryo at 72 h of development. To validate the model and elucidate various underlying survival and death mechanisms, we employed imaging (Doppler blood flow imaging), biochemical, and blotting techniques and evaluated the cell death mechanism: autophagy and inflammation caused by I/R. In conclusion, the present model is useful in parallel with established in vitro and in vivo I/R models to understand the mechanisms of I/R development and its treatment.

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“…This may be in concert with baicalein’s ability to reduce ROS, leading to decreased interaction of oxidized Akt with PTEN, thereby promoting Akt activation [ 33 , 34 ]. The activated Akt can downregulate NADPH oxidase, a major source of ROS under both physiological and pathological conditions, via blocking mTOR phosphorylation thereby decreasing ROS generation [ 35 ]. This could be another likely mechanism whereby baicalein reduces ROS generation, other than the possibilities of scavenging ROS or inhibiting Fe 2+ -regulated radical production.…”

Section: Discussionmentioning

confidence: 99%

Baicalein Rescues Delayed Cooling via Preservation of Akt Activation and Akt-Mediated Phospholamban Phosphorylation

Shao

Chen

Zhu

et al. 2018

IJMS

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Cooling reduces the ischemia/reperfusion (I/R) injury seen in sudden cardiac arrest (SCA) by decreasing the burst of reactive oxygen species (ROS). Its cardioprotection is diminished when delay in reaching the target temperature occurs. Baicalein, a flavonoid derived from the root of Scutellaria baicalensis Georgi, possesses antioxidant properties. Therefore, we hypothesized that baicalein can rescue cooling cardioprotection when cooling is delayed. Two murine cardiomyocyte models, an I/R model (90 min ischemia/3 h reperfusion) and stunning model (30 min ischemia/90 min reperfusion), were used to assess cell survival and contractility, respectively. Cooling (32 °C) was initiated either during ischemia or during reperfusion. Cell viability and ROS generation were measured. Cell contractility was evaluated by real-time phase-contrast imaging. Our results showed that cooling reduced cell death and ROS generation, and this effect was diminished when cooling was delayed. Baicalein (25 µM), given either at the start of reperfusion or start of cooling, resulted in a comparable reduction of cell death and ROS production. Baicalein improved phospholamban phosphorylation, contractility recovery, and cell survival. These effects were Akt-dependent. In addition, no synergistic effect was observed with the combined treatments of cooling and baicalein. Our data suggest that baicalein may serve as a novel adjunct therapeutic strategy for SCA resuscitation.

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Maternal diabetes up‐regulates NOX2 and enhances myocardial ischaemia/reperfusion injury in adult offspring

Cited by 13 publications

References 45 publications

Exosomes Released from CaSR‐Stimulated PMNs Reduce Ischaemia/Reperfusion Injury

Exosomes Released from CaSR‐Stimulated PMNs Reduce Ischaemia/Reperfusion Injury

Chick Embryo: A Preclinical Model for Understanding Ischemia-Reperfusion Mechanism

Baicalein Rescues Delayed Cooling via Preservation of Akt Activation and Akt-Mediated Phospholamban Phosphorylation

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