scholarly journals β-Sitosterol Protects against Myocardial Ischemia/Reperfusion Injury via Targeting PPARγ/NF-κB Signalling

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Fengxia Lin ◽  
Luhua Xu ◽  
Meizhu Huang ◽  
Bin Deng ◽  
Weiwei Zhang ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Peroxisome Proliferator ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia/reperfusion (I/R) injury is a clinically severe complication, which can cause high rates of disability and mortality particularly in patients with myocardial infarction, yet the molecular mechanisms underlying this process remain unclear. This study aimed to explore the protective effects of β-sitosterol against myocardial I/R injury and to elucidate the underlying molecular mechanisms. Our results showed that hypoxia/reoxygenation (H/R) treatment suppressed cell viability, induced cell apoptosis and reactive oxygen species production, increased caspase-3 and -9 activities, upregulated caspase-3 and -9 protein expressions, downregulated the Bcl-2 protein expression, and reduced the mitochondrial membrane potential. β-Sitosterol treatment attenuated H/R-induced cardiomyocyte injury. Moreover, β-sitosterol treatment counteracted the inhibitory effects of H/R treatment on the peroxisome proliferator-activated receptor gamma (PPARγ) expression and enhanced effects of H/R treatment on the NF-κB expression in cardiomyocytes. Furthermore, inhibition of PPARγ impaired the protective actions of β-sitosterol against H/R-induced cardiomyocyte injury. In the I/R rats, β-sitosterol treatment reduced the myocardial infarcted size and apoptosis, which was attenuated by the inhibition of PPARγ. In conclusion, our results demonstrate that β-sitosterol protected against in vitro H/R-induced cardiomyocyte injury and in vivo myocardial I/R injury. The β-sitosterol-mediated cardioprotective effects may involve the modulation of PPARγ/NF-κB signalling during myocardial I/R injury. Further studies are required to further explore the clinical application of β-sitosterol in the myocardial I/R injury.

The cardioprotection of dihydrotanshinone I against myocardial ischemia–reperfusion injury via inhibition of arachidonic acid ω-hydroxylase

2016 ◽  
Vol 94 (12) ◽  
pp. 1267-1275 ◽  
Author(s):  
Yidan Wei ◽  
Meijuan Xu ◽  
Yi Ren ◽  
Guo Lu ◽  
Yangmei Xu ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Arachidonic acid (AA) is a precursor that is metabolized by several enzymes to many biological eicosanoids. Accumulating data indicate that the ω-hydroxylation metabolite of AA, 20-hydroxyeicosatetraenoic acid (20-HETE), is considered to be involved in the myocardial ischemia–reperfusion injury (MIRI). The inhibitors of AA ω-hydroxylase, however, are demonstrated to exhibit protective effects on MIRI. Dihydrotanshinone I (DI), a bioactive constituent of danshen, is proven to be a potent inhibitor of AA ω-hydroxylase by our preliminary study in vitro. The purpose of the present study was to investigate the cardioprotection of DI against MIRI and its effects on the concentrations of 20-HETE in vivo. Rats subjected to 30 min of ischemia followed by 24 h of reperfusion were assigned to intravenously receive vehicle (sham and ischemia–reperfusion), low (1 mg/kg), middle (2 mg/kg), or high (4 mg/kg) doses of DI before reperfusion. The results demonstrated that DI treatment could improve cardiac function, reduce infarct size, ameliorate the variations in myocardial zymogram and histopathological disorders, decrease 20-HETE generation, and regulate apoptosis-related protein in myocardial ischemia–reperfusion rats. These findings suggested DI could exert considerable cardioprotective action on MIRI by the attenuation of 20-HETE generation, subsequent myocardial injury, and apoptosis through inhibition on AA ω-hydroxylase.

scholarly journals Calenduloside E Ameliorates Myocardial Ischemia-Reperfusion Injury through Regulation of AMPK and Mitochondrial OPA1

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Min Wang ◽  
Rui-ying Wang ◽  
Jia-hui Zhou ◽  
Xue-heng Xie ◽  
Gui-bo Sun ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Mitochondrial Dynamics ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Calenduloside E (CE) is a natural triterpenoid saponin isolated from Aralia elata (Miq.) Seem., a well-known traditional Chinese medicine. Our previous studies have shown that CE exerts cardiovascular protective effects both in vivo and in vitro. However, its role in myocardial ischemia/reperfusion injury (MIRI) and the mechanism involved are currently unknown. Mitochondrial dynamics play a key role in MIRI. This study investigated the effects of CE on mitochondrial dynamics and the signaling pathways involved in myocardial ischemia/reperfusion (MI/R). The MI/R rat model and the hypoxia/reoxygenation (H/R) cardiomyocyte model were established in this study. CE exerted significant cardioprotective effects in vivo and in vitro by improving cardiac function, decreasing myocardial infarct size, increasing cardiomyocyte viability, and inhibiting cardiomyocyte apoptosis associated with MI/R. Mechanistically, CE restored mitochondrial homeostasis against MI/R injury through improved mitochondrial ultrastructure, enhanced ATP content and mitochondrial membrane potential, and reduced mitochondrial permeability transition pore (MPTP) opening, while promoting mitochondrial fusion and preventing mitochondrial fission. However, genetic silencing of OPA1 by siRNA abolished the beneficial effects of CE on cardiomyocyte survival and mitochondrial dynamics. Moreover, we demonstrated that CE activated AMP-activated protein kinase (AMPK) and treatment with the AMPK inhibitor, compound C, abolished the protective effects of CE on OPA1 expression and mitochondrial function. Overall, this study demonstrates that CE is effective in mitigating MIRI by modulating AMPK activation-mediated OPA1-related mitochondrial fusion.

scholarly journals Anastatin Derivatives Alleviate Myocardial Ischemia-Reperfusion Injury via Antioxidative Properties

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4779
Author(s):  
Ying Fu ◽  
Cai Zhao ◽  
Rengui Saxu ◽  
Chaoran Yao ◽  
Lianbo Zhao ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Antioxidant Activities ◽  
Ischemia Reperfusion ◽  
Radical Scavenging ◽  
Serum Lactate Dehydrogenase ◽  
Antioxidant Power ◽  
Myocardial Ischemia Reperfusion

(±)-Anastatins A and B are flavonoids isolated from Anastatica hierochuntica. In a previous study, twenty-four di- and tri-substituted novel derivatives of anastatins were designed and their preliminary antioxidant activities were evaluated. In the present study, the protective effect of myocardial ischemia-reperfusion (I/R) and the systematic antioxidant capacity of 24 derivatives were further studied. Compound 13 was the most potent among all the compounds studied, which increased the survival of H9c2 cells to 80.82%. The antioxidant capability of compound 13 was evaluated in ferric reducing antioxidant power, 2,2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-picrylhydrazyl assays. It was observed that compound 13 significantly reduced infarcted areas and improved histopathological and electrocardiogram changes in rats with myocardial I/R injury. Moreover, compound 13 decreased the leakage rates of serum lactate dehydrogenase, creatine kinase, and malonyldialdehyde from rat myocardial tissues and increased the level of glutathione and superoxide dismutase activities following myocardial I/R injury in rats. Taken together, we concluded that compound 13 had potent cardioprotective effects against myocardial I/R injury both in vitro and in vivo owing to its extensive antioxidant activities.

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.

MicroRNA-141 regulates the expression level of ICAM-1 on endothelium to decrease myocardial ischemia-reperfusion injury

2015 ◽  
Vol 309 (8) ◽  
pp. H1303-H1313 ◽  
Author(s):  
Rong Rong Liu ◽  
Jun Li ◽  
Jiu Yu Gong ◽  
Fang Kuang ◽  
Jia Yun Liu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Cells ◽  
Expression Level ◽  
Novel Target ◽  
Myocardial Ischemia Reperfusion

A growing number of studies have suggested microRNAs (miRNAs) are involved in the modulation of myocardial ischemia-reperfusion (MI/R) injury; however, the role of endogenous miRNAs targeting endothelial cells (ECs) and its interaction with ICAM-1 in the setting of MI/R remain poorly understood. Our microarray results showed that miR-146a, miR-146b-5p, miR-155*, miR-155, miR-497, and miR-451 were significantly upregulated, whereas, miR-141 and miR-564 were significantly downregulated in the ECs challenged with TNF-α for 6 h. Real-time PCR analyses additionally validated that the expression levels of miR-146a, miR-155*, and miR-141 were consistent with the microarray results. Then, ICAM-1 was identified as a novel target of miR-141 by Target Scan software and the reporter gene system. Further functional experiments showed that elevated levels of miR-141 inhibited ICAM-1 expression and diminished leukocytes adhesion to ECs in vitro. In an in vivo murine model of MI/R injury, pretreatment with miR-141 mimics through the tail vein downregulated the expression level of ICAM-1 in heart and attenuated MI/R injury as evidenced by decreased infarct size and decline of serum cardial troponin I (cTnI) and lactate dehydrogenase (LDH) concentration. The cardioprotective effects of miR-141 mimics may be attributed to the decreased infiltration of CD11b+ cells and F4/80+ macrophages into ischemic myocardium tissue. In conclusion, our results demonstrate that miR-141, as a novel repressor of ICAM-1, is involved in the attenuation of MI/R injury via antithetical regulation of ICAM-1 and inflammatory cells infiltration. Thus miR-141 may constitute a new therapeutic target in the setting of ischemic heart disease.

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