scholarly journals The Protective Effect of Cyanidin-3-Glucoside on Myocardial Ischemia-Reperfusion Injury through Ferroptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-15 ◽  
Author(s):  
Xin Shan ◽  
Zhi-Yang Lv ◽  
Meng-Jiao Yin ◽  
Jing Chen ◽  
Jie Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Protective Effect ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
H9c2 Cells ◽  
St Segment Elevation ◽  
Myocardial Ischemia Reperfusion

This study was conducted to estimate the protective effect of Cyanidin-3-glucoside (C3G) on myocardial ischemia-reperfusion (IR) injury and to explore its mechanism. The rats were subjected to left anterior descending ligation and perfusion surgery. In vitro experiments were performed on H9c2 cells using the oxygen-glucose deprivation/reoxygenation (OGD/R) model. The results showed the administration of C3G reduced the infarction area, mitigated pathological alterations, inhibited ST segment elevation, and attenuated oxidative stress and ferroptosis-related protein expression. C3G also suppressed the expressions of USP19, Beclin1, NCOA4, and LC3II/LC3I. In addition, treatment with C3G relieved oxidative stress, downregulated LC3II/LC3I, reduced autophagosome number, downregulated TfR1 expression, and upregulated the expressions of FTH1 and GPX4 in OGD/R-induced H9c2 cells. C3G could inhibit the protein levels of USP19 and LC3II. C3G promoted K11-linked ubiquitination of Beclin1. Further evidence that C3G reduced ferroptosis and ameliorated myocardial I/R injury was demonstrated with the ferroptosis promoter RSL3. Taken together, C3G could be a potential agent to protect myocardium from myocardial I/R injury.

scholarly journals Inhibition of HDAC6 Activity Alleviates Myocardial Ischemia/Reperfusion Injury in Diabetic Rats: Potential Role of Peroxiredoxin 1 Acetylation and Redox Regulation

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Yan Leng ◽  
Yang Wu ◽  
Shaoqing Lei ◽  
Bin Zhou ◽  
Zhen Qiu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Protective Effect ◽  
Redox Regulation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
H9c2 Cells ◽  
Peroxiredoxin 1 ◽  
Myocardial Ischemia Reperfusion

Patients with diabetes are more vulnerable to myocardial ischemia/reperfusion (MI/R) injury, which is associated with excessive reactive oxygen species (ROS) generation and decreased antioxidant defense. Histone deacetylase 6 (HDAC6), a regulator of the antioxidant protein peroxiredoxin 1 (Prdx1), is associated with several pathological conditions in the cardiovascular system. This study investigated whether tubastatin A (TubA), a highly selective HDAC6 inhibitor, could confer a protective effect by modulating Prdx1 acetylation in a rat model of MI/R and an in vitro model of hypoxia/reoxygenation (H/R). Here, we found that diabetic hearts with excessive HDAC6 activity and decreased acetylated-Prdx1 levels were more vulnerable to MI/R injury. TubA treatment robustly improved cardiac function, reduced cardiac infarction, attenuated ROS generation, and increased acetylated-Prdx1 levels in diabetic MI/R rats. These results were further confirmed by an in vitro study using H9c2 cells. Furthermore, a study using Prdx1 acetyl-silencing mutants (K197R) showed that TubA only slightly attenuated H/R-induced cell death and ROS generation in K197R-transfected H9c2 cells exposed to high glucose (HG), but these differences were not statistically significant. Taken together, these findings suggest that HDAC6 inhibition reduces ROS generation and confers a protective effect against MI/R or H/R injury by modulating Prdx1 acetylation at K197.

scholarly journals Mangiferin Attenuates Myocardial Ischemia-Reperfusion Injury via MAPK/Nrf-2/HO-1/NF-κB In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Kun Liu ◽  
Fei Wang ◽  
Shuo Wang ◽  
Wei-Nan Li ◽  
Qing Ye
Keyword(s):  
Oxidative Stress ◽  
Coronary Artery ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cells ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

The aim of this study was to investigate the cardioprotective effect of mangiferin (MAF) in vitro and in vivo. Oxidative stress and inflammatory injury were detected in coronary artery ligation in rats and also in hypoxia-reoxygenation- (H/R-) induced H9c2 cells. MAF inhibited myocardial oxidative stress and proinflammatory cytokines in rats with coronary artery occlusion. The ST segment of MAF treatment groups also resumed. Triphenyltetrazolium chloride (TTC) staining and pathological analysis showed that MAF could significantly reduce myocardial injury. In vitro data showed that MAF could improve hypoxia/reoxygenation- (H/R-) induced H9c2 cell activity. In addition, MAF could significantly reduce oxidative stress and inflammatory pathway protein expression in H/R-induced H9c2 cells. This study has clarified the protective effects of MAF on myocardial injury and also confirmed that oxidative stress and inflammation were involved in the myocardial ischemia-reperfusion injury (I/R) model.

scholarly journals Naringenin Attenuates Myocardial Ischemia-Reperfusion Injury via cGMP-PKGIα Signaling and In Vivo and In Vitro Studies

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Li-Ming Yu ◽  
Xue Dong ◽  
Jian Zhang ◽  
Zhi Li ◽  
Xiao-Dong Xue ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Er Stress ◽  
Ischemia Reperfusion Injury ◽  
Heart Function ◽  
Ischemia Reperfusion ◽  
Guanosine Monophosphate ◽  
Myocardial Ischemia Reperfusion

Endoplasmic reticulum (ER) stress and oxidative stress contribute greatly to myocardial ischemia-reperfusion (MI/R) injury. Naringenin, a flavonoid derived from the citrus genus, exerts cardioprotective effects. However, the effects of naringenin on ER stress as well as oxidative stress under MI/R condition and the detailed mechanisms remain poorly defined. This study investigated the protective effect of naringenin on MI/R-injured heart with a focus on cyclic guanosine monophosphate- (cGMP-) dependent protein kinase (PKG) signaling. Sprague-Dawley rats were treated with naringenin (50 mg/kg/d) and subjected to MI/R surgery with or without KT5823 (2 mg/kg, a selective inhibitor of PKG) cotreatment. Cellular experiment was conducted on H9c2 cardiomyoblasts subjected to simulated ischemia-reperfusion treatment. Before the treatment, the cells were incubated with naringenin (80 μmol/L). PKGIα siRNA was employed to inhibit PKG signaling. Our in vivo and in vitro data showed that naringenin effectively improved heart function while it attenuated myocardial apoptosis and infarction. Furthermore, pretreatment with naringenin suppressed MI/R-induced oxidative stress as well as ER stress as evidenced by decreased superoxide generation, myocardial MDA level, gp91phox expression, and phosphorylation of PERK, IRE1α, and EIF2α as well as reduced ATF6 and CHOP. Importantly, naringenin significantly activated myocardial cGMP-PKGIα signaling while inhibition of PKG signaling with KT5823 (in vivo) or siRNA (in vitro) not only abolished these actions but also blunted naringenin’s inhibitory effects against oxidative stress and ER stress. In summary, our study demonstrates that naringenin treatment protects against MI/R injury by reducing oxidative stress and ER stress via cGMP-PKGIα signaling. Its cardioprotective effect deserves further clinical study.

scholarly journals 20(S)-Ginsenoside Rg2 attenuates myocardial ischemia/reperfusion injury by reducing oxidative stress and inflammation: role of SIRT1

RSC Advances ◽  
2018 ◽  
Vol 8 (42) ◽  
pp. 23947-23962 ◽  
Author(s):  
Wenwen Fu ◽  
Huali Xu ◽  
Xiaofeng Yu ◽  
Chen Lyu ◽  
Yuan Tian ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

20(S)-Ginsenoside Rg2 confers a protective effect against MI/R injury via SIRT1 signaling, by alleviating oxidative stress and reducing myocardium inflammation.

Up-regulation of CTRP12 ameliorates hypoxia/re-oxygenation-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling

2021 ◽  
pp. 096032712110218
Author(s):  
Ai-Ping Jin ◽  
Qian-Rong Zhang ◽  
Cui-Ling Yang ◽  
Sha Ye ◽  
Hai-Juan Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Target Genes ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Artery Disease ◽  
Myocardial Ischemia Reperfusion

C1q/TNF-related protein 12 (CTRP12) has been reported to play a key role in coronary artery disease. However, whether CTRP12 plays a role in the regulation of myocardial ischemia-reperfusion injury is not fully understood. The goals of this work were to assess the possible relationship between CTRP12 and myocardial ischemia-reperfusion injury. Here, we exposed cardiomyocytes to hypoxia/re-oxygenation (H/R) to establish an in vitro cardiomyocyte injury model of myocardial ischemia-reperfusion injury. Our results showed that H/R treatment resulted in a decrease in CTRP12 expression in cardiomyocytes. The up-regulation of CTRP12 ameliorated H/R-induced cardiomyocyte injury via the down-regulation of apoptosis, oxidative stress, and inflammation. In contrast, the knockdown of CTRP12 enhanced cardiomyocyte sensitivity to H/R-induced cardiomyocyte injury. Further investigation showed that CTRP12 enhanced the levels of nuclear Nrf2 and increased the expression of Nrf2 target genes in cardiomyocytes exposed to H/R. However, the inhibition of Nrf2 markedly diminished CTRP12-overexpression-mediated cardioprotective effects against H/R injury. Overall, these data indicate that CTRP12 protects against H/R-induced cardiomyocyte injury by inhibiting apoptosis, oxidative stress, and inflammation via the enhancement of Nrf2 signaling. This work suggests a potential role of CTRP12 in myocardial ischemia-reperfusion injury and proposes it as an attractive target for cardioprotection.

scholarly journals Downregulated MicroRNA-327 Attenuates Oxidative Stress–Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Tao Zheng ◽  
Jun Yang ◽  
Jing Zhang ◽  
Chaojun Yang ◽  
Zhixing Fan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ros Generation ◽  
Nrf2 Signaling Pathway ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Although miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxidative stress and cardiomyocytes injury were detected in rat model of MI/RI, hypoxia/reoxygenation (H/R), and tert-butyl hydroperoxide (TBHP) model of H9c2 cells. In vitro, downregulation of miR-327 inhibited both H/R- and TBHP-induced oxidative stress, and suppressed apoptosis. Meanwhile, fibroblast growth factor 10(FGF10) was enhanced by miR-327 knocked down, followed by the activation of p-PI3K and p-Akt, and the translocation of Nrf2. However, miR-327 overexpression performed with opposite effects. Consistent with the results in vitro, downregulation of miR-327 attenuated reactive oxygen species (ROS) generation as well as intrinsic apoptosis, and alleviated I/R injury. In conclusion, inhibition of miR-327 improved antioxidative ability and myocardial cell survival via regulating the FGF10/Akt/Nrf2 pathway.

MicroRNA-760-mediated low expression of DUSP1 impedes the protective effect of NaHS on myocardial ischemia–reperfusion injury

2020 ◽  
Vol 98 (3) ◽  
pp. 378-385
Author(s):  
Lin Ren ◽  
Qian Wang ◽  
Lixiang Ma ◽  
Dongmei Wang
Keyword(s):  
Myocardial Ischemia ◽  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cells ◽  
Expression Levels ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Low Expression

Myocardial ischemia–reperfusion injury (MIRI) is the leading cause of the poor prognosis for patients undergoing clinical cardiac surgery. Micro-RNAs are involved in MIRI; however, the effect of miR-760 on MIRI and the molecular mechanisms behind it have not yet been described. For our in-vivo experiments, 20 rats were randomly distributed between 2 groups (n = 10): the sham-treatment group and the ischemia–reperfusion (I/R) group. For our in-vitro experiments, H9C2 cells were subjected to hypoxia for 6 h, and then reoxygenated to establish an hypoxia–reoxygenation (H/R) model. High expression levels of of miR-760 were observed in the rats subjected to MIRI and the H9C2 cells subjected to H/R. Further, the levels of lactate dehydrogenase (LDH) and malonaldehyde (MDA) were increased, and the size of the myocardial infarct was notably greater in the rats subjected to MIRI, suggesting that miR-760 worsens the effects of MIRI. The inhibitory effects from NaHS on apoptosis were enhanced, as were the expression levels of cleaved caspase 3 and cleaved PARP in H9C2 cells exposed to H/R, and with low-expression levels of miR-760. TargetScan and dual luciferase reporter assays further confirmed the targeted relationship between dual-specificity protein phosphatase (DUSP1) and miR-760. Additionally, miR-760 overexpression and H/R treatment of H9C2 cells inhibited the expression of DUSP1, which further promoted apoptosis. Furthermore, DUSP1 enhanced the anti-apoptotic effects of NaHS in rats subjected to MIRI. Taken together, these findings suggest that miR-760 inhibits the protective effect of NaHS against MIRI.

scholarly journals The Exosomal lncRNA KLF3-AS1 From Ischemic Cardiomyocytes Mediates IGF-1 Secretion by MSCs to Rescue Myocardial Ischemia-Reperfusion Injury

2021 ◽  
Vol 8 ◽  
Author(s):  
Gecai Chen ◽  
Aihuan Yue ◽  
Meixiang Wang ◽  
Zhongbao Ruan ◽  
Li Zhu
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
H9c2 Cell ◽  
H9c2 Cells ◽  
Myocardial Ischemia Reperfusion

The purpose of the study was to explore the mechanism by which myocardial ischemia-reperfusion (I/R) injury-induced exosomes modulate mesenchymal stem cells (MSCs) to regulate myocardial injury. In this study, we established an I/R injury model in vivo and a hypoxia-reoxygenation (H/R) model in vitro. Then, exosomes isolated from H/R-exposed H9c2 cells were characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot analysis. CCK-8 assays and flow cytometry were performed to assess cell injury. ELISA was applied to determine the level of insulin-like growth factor 1 (IGF-1). Echocardiography was used to assess cardiac function in vivo. HE staining and TUNEL assays were conducted to analyze myocardial injury in vivo. In the present study, H/R-exposed H9c2 cells induced IGF-1 secretion from MSCs to inhibit cell myocardial injury. Moreover, exosomes derived from H/R-exposed H9c2 cells were introduced to MSCs to increase IGF-1 levels. The lncRNA KLF3-AS1 was dramatically upregulated in exosomes derived from H/R-treated H9c2 cells. Functional experiments showed that the exosomal lncRNA KLF3-AS1 promoted IGF-1 secretion from MSCs and increased H9c2 cell viability. In addition, miR-23c contains potential binding sites for both KLF3-AS1 and STAT5B, and miR-23c directly bound to the 3'-UTRs of KLF3-AS1 and STAT5B. Furthermore, the lncRNA KLF3-AS1 promoted IGF-1 secretion from MSCs and rescued myocardial cell injury in vivo and in vitro by upregulating STAT5B expression. The lncRNA KLF3-AS1 may serve as a new direction for the treatment of myocardial I/R injury.

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