scholarly journals Kaempferide Protects against Myocardial Ischemia/Reperfusion Injury through Activation of the PI3K/Akt/GSK-3β Pathway

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Dong Wang ◽  
Xinjie Zhang ◽  
Defang Li ◽  
Wenjin Hao ◽  
Fanqing Meng ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Related Factor ◽  
Dependent Manner ◽  
Expression Levels ◽  
Myocardial Ischemia Reperfusion

The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner. In addition, preconditioning treatment with Kae was found to significantly decrease serum TNF-α, IL-6, C-reactive protein (CRP), MDA, and ROS levels, while it was found to increase serum levels of SOD. Nuclear factor erythroid 2-related factor 2 (Nrf2) and cleaved caspase-3 expression levels were observed to be downregulated, while phospho-Akt (p-Akt) and phospho-glycogen synthase kinase-3β (p-GSK-3β) expression levels were upregulated. However, cotreatment with LY294002 (a PI3K inhibitor) or TDZD-8 (a GSK-3β inhibitor) was found to abolish the above cardioprotective effects observed with the Kae treatment. The data presented in this study provides evidence that Kae attenuates I/R-induced myocardial injury through inhibition of the Nrf2 and cleaved caspase-3 signaling pathways via a PI3K/Akt/GSK 3β-dependent mechanism.

scholarly journals The Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of the Bauhinia Championii Flavone are Connected with Protection Against Myocardial Ischemia/Reperfusion Injury

2016 ◽  
Vol 38 (4) ◽  
pp. 1365-1375 ◽  
Author(s):  
Jie Jian ◽  
Feifei Xuan ◽  
Feizhang Qin ◽  
Renbin Huang
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Previous studies have demonstrated that Bauhinia championii flavone (BCF) exhibits anti-oxidative, anti-hypoxic and anti-stress properties. This study was designed to investigate whether BCF has a cardioprotective effect against myocardial ischemia/reperfusion (I/R) injuries in rats and to shed light on its possible mechanism. Methods: The model of I/R was established by ligating the left anterior descending coronary artery for 30 min, then reperfusing for 180 min. Hemodynamic changes were continuously monitored. The content of malondialdehyde (MDA) as well as the lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. The release of interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis of cardiomyocytes was determined by caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of TLR4, NF-κBp65, Bcl-2 and Bax were detected by western blotting. Results: Pretreatment with BCF significantly reduced the serum levels of LDH, MDA and IL-6, but increased the activities of SOD and GSH-Px. It also attenuated myocardial infarct size, reduced the apoptosis rate and preserved cardiac function. Furthermore, BCF inhibited caspase-3 activity and the expression of TLR4, phosphorylated NF-κBp65 and Bax, but enhanced the expression of Bcl-2. Conclusion: These results provide substantial evidence that BCF exerts a protective effect on myocardial I/R injury, which may be attributed to attenuating lipid peroxidation, the inflammatory response and apoptosis.

scholarly journals STAT3 but Not STAT5 Contributes to the Protective Effect of Electroacupuncture Against Myocardial Ischemia/Reperfusion Injury in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui-Hui Guo ◽  
Xin-Yue Jing ◽  
Hui Chen ◽  
Hou-Xi Xu ◽  
Bing-Mei Zhu
Keyword(s):  
Myocardial Ischemia ◽  
Protective Effect ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Coronary Artery Ligation ◽  
Myocardial Infarct Size ◽  
Dependent Manner ◽  
Stat3 Signaling ◽  
Gene And Protein Expression ◽  
Myocardial Ischemia Reperfusion

Electroacupuncture (EA) can help reduce infarct size and injury resulting from myocardial ischemia/reperfusion (I/R); however, the underlying molecular mechanism remains unknown. We previously reported that STAT5 plays a critical role in the cardioprotective effect of remote ischemic preconditioning (RIPC). Here, we assessed the effects of electroacupuncture pretreatment (EAP) on myocardial I/R injury in the presence and/or absence of Stat5 in mice and investigated whether EAP exerts its cardioprotective effects in a STAT5-dependent manner. Adult Stat5fl/fl and Stat5-cKO mice were exposed to EAP at Neiguan (PC6) for 7 days before the induction of I/R injury by left anterior descending (LAD) coronary artery ligation. The myocardial infarct size (IS), area at risk, and apoptotic rate of cardiomyocytes were detected. RT-qPCR and western blotting were used to measure gene and protein expression, respectively, in homogenized heart tissues. RNA-seq was used to identify candidate genes and pathways. Our results showed that EAP decreased IS and the rate of cardiomyocyte apoptosis. We further found that STAT5 was activated by EAP in Stat5fl/fl mice but not in Stat5-cKO mice, whereas the opposite was observed for STAT3. Following EAP, the levels of the antiapoptotic proteins Bcl-xL, Bcl-2, and p-AKT were increased in the presence of Stat5, while that of interleukin 10 (IL-10) was increased in both Stat5fl/fl and Stat5-cKO. The gene expression profile in heart tissues was different between Stat5fl/fl and the Stat5-cKO mice with EAP. Importantly, the top 30 DEGs under EAP in the Stat5-cKO mice were enriched in the IL-6/STAT3 signaling pathway. Our results revealed for the first time that the protective effect of EAP following myocardial I/R injury was attributable to, but not dependent on, STAT5. Additionally, we found that EAP could activate STAT3 signaling in the absence of the Stat5 gene, and could also activate antiapoptotic, survival, and anti-inflammatory signaling pathways.

scholarly journals Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mingjie Zhou ◽  
Huanhuan Ren ◽  
Jichun Han ◽  
Wenjuan Wang ◽  
Qiusheng Zheng ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Cytochrome C ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Glycogen Synthase Kinase ◽  
Myocardial Ischemia Reperfusion

Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats.Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β(GSK-3β), phospho-GSK-3β(P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis.Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and±dp/dtmax, as well as increased the levels of SOD and P-GSK-3βand GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α.Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3βactivity in rats with I/R.

scholarly journals The Blockade of Transmembrane Cl- Flux Mitigates I/R-Induced Heart Injury via the Inhibition of Calpain Activity

2015 ◽  
Vol 35 (6) ◽  
pp. 2121-2134 ◽  
Author(s):  
Jian-Ying Zhang ◽  
Feng Wu ◽  
Xiao-Ming Gu ◽  
Zhen-Xiao Jin ◽  
Ling-Heng Kong ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Calpain Activity ◽  
Rat Hearts ◽  
Marked Decline ◽  
Heart Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Injury Area

Aims: The aim of this study was to determine whether calpain is involved in Cl- -induced myocardial ischemia/reperfusion (I/R) injury. Methods: Isolated rat hearts were subjected to either 45 min of global no-flow ischemia followed by reperfusion or successive perfusion with Ca2+ -free KH solution for 3 min and normal KH solution for 30 min, also known as Ca2+ paradox. Results: The hearts in the I/R group exhibited increases in myocardial injury area, LDH release, caspase 3 activity and apoptotic indices and a marked decline in cardiac performance. As was the case regarding the effects of MDL 28170, an inhibitor of calpain, treatment with 5 µM NPPB, 5 µM DIDS and low Cl- significantly attenuated cardiac injury. Moreover, each of the treatments significantly protected against Ca2+ overload-induced injury in the setting of Ca2+ paradox. The Western blot and immunofluorescence data revealed that there was an increase in the percentages of calpain membrane-positive cells and the numbers of fragments resulting from the calpain-mediated proteolysis of α-fodrin in both the I/R and the Ca2+ paradox, indicating that the activation of calpain occurred. More importantly, these effects were mitigated by the blockade of transmembrane Cl- flux, as was accomplished via MDL 28170. Conclusion: Our results provide evidence that the blockade of transmembrane Cl- flux mitigates I/R-induced cardiac injury via the inhibition of calpain activity. They also indicate that intracellular Ca2+ overload regulates calpain activation in the setting of Cl- -induced injury.

scholarly journals The expression and role of β3AR protein in myocardial ischemia/reperfusion in rats

2021 ◽  
Author(s):  
Zi-Long Wang ◽  
Xiao-Chen Sun ◽  
Rong Luo ◽  
Dong-Ye Li ◽  
Hao-Chen Xuan
Keyword(s):  
Myocardial Ischemia ◽  
Protein Expression ◽  
Caspase 3 ◽  
Sham Group ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Sd Rats ◽  
Group I ◽  
Myocardial Ischemia Reperfusion

IntroductionTo explore serum norepinephrine (NE) concentration and β3-adrenoceptor (β3AR) protein expression at different times during myocardial ischemia/reperfusion (I/R) and examine the role of β3AR in I/R.Material and methods28 Sprague-Dawley (SD) rats were randomly divided into one sham group and six I/R groups. The rats in the I/R groups were subjected to ischemia for 45 minutes. After reperfusion, the serum NE concentration and the β3AR protein expression in the myocardial tissue of the left ventricular injury region were detected. Another 18 SD rats were randomly divided into a sham group, I/R groups, and I/R + BRL37344 group.ResultsCompared with the sham group, the serum NE concentration of rats in the I/R groups significantly increased at 6 hours (P < 0.001). The serum NE concentration and myocardial β3AR protein expression were both highest at 72 hours. Compared with the sham group, the expressions of the pro-apoptotic proteins Bax and cleaved caspase-3 after I/R were significantly increased (P < 0.01, P < 0.001, respectively), and the expression of anti-apoptotic protein Bcl-2 was significantly decreased (P < 0.01). Compared with I/R groups, the expressions of Bax and cleaved caspase-3 in the I/R + BRL37344 group were significantly decreased (P < 0.05, P < 0.01, respectively).ConclusionsWith the prolongation of myocardial I/R in rats, serum NE concentration and β3AR protein expression showed a significant increase trend and reached a peak at 72 hours. Specific β3AR agonist BRL37344 can reduce myocardial I/R injury in vivo in rats, alleviate apoptosis, reduce infarct size, and improve cardiac function.

Abstract 16381: Novel Thiol-activated H2S Donors Attenuate Myocardial Ischemia/Reperfusion Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Chelsea Organ ◽  
Zhen Li ◽  
Yu Zhao ◽  
Chuntao Yang ◽  
Shashi Bhushan ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Sustained Release ◽  
Murine Model ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background: Hydrogen sulfide (H2S) protects against acute myocardial ischemia/reperfusion (MI/R) injury and heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. One of the major limitations of currently available H2S donors is poor pharmacokinetics profiles that result in very rapid and uncontrolled H2S release. NSHD-1 and NSHD-2 are recently developed thiol-activated H2S donors designed for sustained release of H2S upon activation by molecules containing thiol groups such as cysteine and glutathione. We hypothesized that these novel H2S donors would generate H2S for extended periods and ameliorate myocardial cell death following MI/R in an in vivo murine model. Methods and Results: C57BL6/J male mice (10-12 weeks of age) were subjected to 45 minutes of MI followed by 24 hours of R. At the time of reperfusion, animals received Vehicle (0.5% THF), NSHD-1 (50 μg/kg and 100 μg/kg), or NSHD-2 (50 μg/kg) by direct intracardiac (i.c.) injection. In addition, at 4 hours of R, plasma was collected for troponin-I measurements. In preliminary studies we observed sustained release of H2S with both of these H2S donors. Myocardial infarct size was reduced by 35% (p < 0.01 vs. Vehicle) in mice treated with NSHD-1 (100 μg/kg), 43% (p < 0.05 vs. Vehicle) in mice treated with NSHD-2 (50 μg/kg), and 54% (p < 0.01 vs. Vehicle) in mice treated with NSHD-2 (100 μg/kg). Conclusions: NSHD-1 and NSHD-2 significantly attenuate MI/R injury in a murine model. Experiments are currently underway to further define the in vivo pharmacokinetics of H2S release from these agents, mechanisms of action, and safety profile.

scholarly journals Daucosterol pretreatment ameliorates myocardial ischemia reperfusion injury via ROS-mediated NLRP3 inflammasome activation

2020 ◽  
Vol 19 (5) ◽  
pp. 1031-1036
Author(s):  
Guixiang Zhao ◽  
Xiaoyun Ma ◽  
Juledezi Hailati ◽  
Zhen Bao ◽  
Maerjiaen Bakeyi ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Inflammasome Activation ◽  
Myocardial Infarct Size ◽  
Nlrp3 Inflammasome Activation ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Purpose: To determine the involvement of NLRP3 signaling pathway in the preventive role of daucosterol in acute myocardial infarction (AMI).Methods: H9C2 cells were pretreated with daucosterol before hypoxia/reoxygenation (HR) injury. Myocardial ischemia reperfusion (IR) was established in male SD rats, followed by reperfusion. Myocardial infarct size was measured. The serum levels of creatine kinase (CK), lactate  dehydrogenase (LDH), total superoxide dismutase (T-SOD), and malondialdehyde (MDA) were determined using commercial kits. NLRP3 inflammasome activation was assessed by western blotting.Results: Myocardial infarct size was smaller after IR injury in rats pretreated with daucosterol (10 and 50 mg/kg) than that pretreated with daucosterol (0 and 1 mg/kg). The increase in LDH, CK, and MDA levels after IR injury was reduced following daucosterol pretreatment. Reactive oxygen species (ROS) production increased, whereas T-SOD activity decreased after IR injury. These changes were prevented by pretreatment of daucosterol (10 and 50 mg/kg). Protein expression of NLRP3 inflammasome increased after IR injury in H9C2 cells while pretreatment with daucosterol inhibited the upregulation of NLRP3 inflammasome.Conclusion: The cardioprotective effect of daucosterol pretreatment appears to be mediated via the inactivation of ROS-related NLRP3 inflammasome, suggesting that daucosteol might be a potential therapeutic drug for AMI. Keywords: Daucosterol, Myocardial ischemia, Reperfusion injury, Reactive oxygen species, NLRP3 inflammasome

TGF-β1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1

2003 ◽  
Vol 284 (5) ◽  
pp. H1612-H1617 ◽  
Author(s):  
Hongjiang Chen ◽  
Dayuan Li ◽  
Tom Saldeen ◽  
Jawahar L. Mehta
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Left Ventricular ◽  
Blue Staining ◽  
Control Group ◽  
Dependent Manner ◽  
Arterial Blood ◽  
Group I

Ischemia-reperfusion (I/R) is thought to upregulate the expression and activity of matrix metalloproteinases (MMPs), which regulate myocardial and vascular remodeling. Previous studies have shown that transforming growth factor-β1 (TGF-β1) can attenuate myocardial injury induced by I/R. TGF-β1 is also reported to suppress the release of MMPs. To study the modulation of MMP-1 by TGF-β1 in I/R myocardium, Sprague-Dawley rats were given saline and subjected to 1 h of myocardial ischemia [total left coronary artery (LCA) ligation] followed by 1 h of reperfusion ( n = 9). Parallel groups of rats were pretreated with recombinant TGF-β1(rTGF-β1, 1 mg/rat, n = 9) before reperfusion or exposure to sham I/R (control group). I/R caused myocardial necrosis and dysfunction, indicated by decreased first derivative of left ventricular pressure, mean arterial blood pressure, and heart rate (all P < 0.01 vs. sham-operated control group). Simultaneously, I/R upregulated MMP-1 ( P < 0.01). Treatment of rats with rTGF-β1 reduced the extent of myocardial necrosis and dysfunction despite I/R (all P < 0.01). rTGF-β1 treatment also inhibited the upregulation of MMP-1 in the I/R myocardium ( P < 0.05). To determine the direct effect of MMP-1 on the myocardium, isolated adult rat myocytes were treated with active MMP-1, which caused injury and death of cultured myocytes, measured as lactate dehydrogenase release and trypan blue staining, in a dose- and time-dependent manner ( P < 0.05). Pretreatment with PD-166793, a specific MMP inhibitor, attenuated myocardial injury and death induced by active MMP-1. The present study for the first time shows that MMP-1 can directly cause myocyte injury or death and that attenuation of myocardial I/R injury by TGF-β1 may, at least partly, be mediated by the inhibition of upregulation of MMP-1.

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