Rosuvastatin Alleviates Coronary Microembolization-Induced Cardiac Injury by Suppressing Nox2-Induced ROS Overproduction and Myocardial Apoptosis

2022 ◽  
Author(s):  
Yuanyuan Cao ◽  
Zhangwei Chen ◽  
Jianguo Jia ◽  
Ao Chen ◽  
Yanhua Gao ◽  
...  
Keyword(s):  
Cardiac Injury ◽  
Coronary Microembolization ◽  
Myocardial Apoptosis

scholarly journals Ligustrazine Attenuates Myocardial Injury Induced by Coronary Microembolization in Rats by Activating the PI3K/Akt Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Qiang Su ◽  
Xiangwei Lv ◽  
Ziliang Ye
Keyword(s):  
Nitric Oxide ◽  
Cardiac Dysfunction ◽  
Myocardial Injury ◽  
Troponin I ◽  
Interleukin 1 ◽  
Akt Pathway ◽  
Local Inflammatory Response ◽  
Coronary Microembolization ◽  
Myocardial Apoptosis ◽  
Phosphorylated Akt

Background/Aims. Coronary microembolization- (CME-) induced myocardial injury and progressive cardiac dysfunction are mainly caused due to CME-induced myocardial local inflammatory response and myocardial apoptosis. Ligustrazine plays an important protective role in multiple cardiovascular diseases, but its role and the protection mechanism in CME is unclear. This study hypothesized that ligustrazine attenuates CME-induced myocardial injury in rats. This study also explored the mechanism underlying this attenuation. Methods. Forty SD rats were randomly divided into CME group, ligustrazine group, ligustrazine+LY294002 (ligustrazine+LY) group, and sham group (ten rats in each). In each group, the cardiac function, apoptotic index, serum c-troponin I (cTnI) level, inflammation [interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α)], and oxidative stress [nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA)] were determined. Western blotting was used to detect the proteins which are present in the PI3K/Akt pathway. Results. Ligustrazine improved cardiac dysfunction induced by CME, increased serum NO and SOD activities, and decreased the serum level in IL-1β, MDA, cTnI, and TNF-α. Moreover, ligustrazine inhibited myocardial apoptosis, which is perhaps caused by the upregulated Bcl-2, the downregulated cleaved caspase-3 and Bax, and the increased protein level in endothelial nitric oxide synthase and phosphorylated Akt. These effects, however, were reduced if ligustrazine was coadministered with LY294002. Conclusions. Ligustrazine attenuates CME-induced myocardial injury. The effects associated with this attenuation may be achieved by activating the myocardium PI3K/Akt signaling pathway.

scholarly journals Exercise Prevents Cardiac Injury and Improves Mitochondrial Biogenesis in Advanced Diabetic Cardiomyopathy with PGC-1α and Akt Activation

2015 ◽  
Vol 35 (6) ◽  
pp. 2159-2168 ◽  
Author(s):  
Hui Wang ◽  
Yihua Bei ◽  
Yan Lu ◽  
Wei Sun ◽  
Qi Liu ◽  
...  
Keyword(s):  
Exercise Training ◽  
Cardiac Function ◽  
Diabetic Cardiomyopathy ◽  
Mitochondrial Biogenesis ◽  
Cardiac Injury ◽  
Akt Signaling ◽  
Cardioprotective Effect ◽  
Mrna Levels ◽  
Myocardial Apoptosis ◽  
Exercise Induced

Background/Aims: Diabetic cardiomyopathy (DCM) represents the major cause of morbidity and mortality among diabetics. Exercise has been reported to be effective to protect the heart from cardiac injury during the development of DCM. However, the potential cardioprotective effect of exercise in advanced DCM remains unclear. Methods: Seven-week old male C57BL/6 wild-type or db/db mice were either subjected to a running exercise program for 15 weeks or kept sedentary. Cardiac function, myocardial apoptosis and fibrosis, and mitochondrial biogenesis were examined for evaluation of cardiac injury. Results: A reduction in ejection fraction and fractional shortening in db/db mice was significantly reversed by exercise training. DCM induced remarkable cardiomyocyte apoptosis and increased ratio of Bax/Bcl-2 at the protein level. Meanwhile, DCM caused slightly myocardial fibrosis with elevated mRNA levels of collagen I and collagen III. Also, DCM resulted in a reduction of mitochondrial DNA (mtDNA) replication and transcription, together with reduced mtDNA content and impaired mitochondrial ultrastructure. All of these changes could be abolished by exercise training. Furthermore, DCM-associated inhibition of PGC-1α and Akt signaling was significantly activated by exercise, indicating that exercise-induced activation of PGC-1α and Akt signaling might be responsible for mediating cardioprotective effect of exercise in DCM. Conclusion: Exercise preserves cardiac function, prevents myocardial apoptosis and fbrosis, and improves mitochondrial biogenesis in the late stage of DCM. Exercise-induced activation of PGC-1α and Akt signaling might be promising therapeutic targets for advanced DCM.

scholarly journals H3 Relaxin Protects Against Myocardial Injury in Experimental Diabetic Cardiomyopathy by Inhibiting Myocardial Apoptosis, Fibrosis and Inflammation

2017 ◽  
Vol 43 (4) ◽  
pp. 1311-1324 ◽  
Author(s):  
Xiaohui Zhang ◽  
Liya Pan ◽  
Kelaier Yang ◽  
Yu Fu ◽  
Yue Liu ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Protein Expression ◽  
Diabetic Cardiomyopathy ◽  
Nlrp3 Inflammasome ◽  
Myocardial Injury ◽  
Cardiac Injury ◽  
Control Group ◽  
Inflammasome Activation ◽  
Protein Levels ◽  
Myocardial Apoptosis

Background/Aims: Apoptosis, fibrosis and NLRP3 inflammasome activation are involved in the development of diabetic cardiomyopathy (DCM). Human recombinant relaxin-3 (H3 relaxin) is a novel bioactive peptide that inhibits cardiac injury; however, whether H3 relaxin prevents cardiac injury in rats with DCM and the underlying mechanisms are unknown. Methods: To investigate the effect of H3 relaxin on DCM, we performed a study using H3 relaxin treatment in male Sprague-Dawley (SD) rats with streptozotocin (STZ)-induced diabetes (DM). We measured apoptosis, fibrosis and NLRP3 inflammasome markers in the rat hearts four and eight weeks after the rats were injected with STZ (65 mg/kg) by western blot analysis. Subsequently, 2 or 6 weeks after the STZ treatment, the rats were treated with H3 relaxin [2 µg/kg/d (A group) or 0.2 µg/kg/d (B group)] for 2 weeks. Cardiac function was evaluated by echocardiography to determine the extent of myocardial injury in the DM rats. The protein levels of apoptosis, fibrosis and NLRP3 inflammasome markers were used to assess myocardial injury. In addition, we determined the plasma levels of IL-1β and IL-18 using a Milliplex MAP Rat Cytokine/Chemokine Magnetic Bead Panel kit. Results: The protein expression of cleaved caspase-8, caspase-9 and caspase-3 as well as fibrosis markers increased at 4 and 8 weeks in the STZ-induced diabetic hearts compared with the levels in the control group. Furthermore, the NLRP3 inflammasome was substantially activated in STZ-induced diabetic hearts, leading to increased IL-1β and IL-18 levels. Compared with the DM group, the A group exhibited substantially better cardiac function. The protein levels of apoptosis markers were attenuated by H3 relaxin, indicating that H3 relaxin inhibited myocardial apoptosis in the hearts of diabetic rats. The protein expression of fibrosis markers was inhibited by H3 relaxin. Additionally, the protein expression and activation of the NLRP3 inflammasome were also effectively attenuated by H3 relaxin. Conclusions: This study is the first to demonstrate that H3 relaxin plays an anti-apoptotic, anti-fibrotic and anti-inflammatory role in DCM.

scholarly journals Resveratrol Pretreatment Inhibits Myocardial Apoptosis in Rats Following Coronary Microembolization via Inducing the PI3K/Akt/GSK-3β Signaling Cascade

2021 ◽  
Vol Volume 15 ◽  
pp. 3821-3834
Author(s):  
Tao Li ◽  
Zhiqing Chen ◽  
You Zhou ◽  
Haoliang Li ◽  
Jian Xie ◽  
...  
Keyword(s):  
Signaling Cascade ◽  
Coronary Microembolization ◽  
Myocardial Apoptosis ◽  
Gsk 3Β

Effect of Atorvastatin (Lipitor) on Myocardial Apoptosis and Caspase-8 Activation Following Coronary Microembolization

2011 ◽  
Vol 61 (2) ◽  
pp. 399-406 ◽  
Author(s):  
Lang Li ◽  
Qiang Su ◽  
Yan Wang ◽  
Rixin Dai ◽  
Yongguang Lu ◽  
...  
Keyword(s):  
Caspase 8 ◽  
Coronary Microembolization ◽  
Myocardial Apoptosis

Atorvastatin Pretreatment Inhibits Myocardial Inflammation and Apoptosis in Swine After Coronary Microembolization

2016 ◽  
Vol 22 (2) ◽  
pp. 189-195
Author(s):  
Jiang-You Wang ◽  
Han Chen ◽  
Xi Su ◽  
You Zhou ◽  
Lang Li
Keyword(s):  
Cardiac Function ◽  
Caspase 3 ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Pathological Examination ◽  
Ventricular Ejection Fraction ◽  
Coronary Microembolization ◽  
Myocardial Apoptosis ◽  
Tnf Α ◽  
Apoptosis And Inflammation

Background/Aim: In addition to its cholesterol-lowering effect, atorvastatin (ATV) has been thought to have multiple cardiovascular benefits, including anti-inflammatory and anti-apoptotic properties. The present study was undertaken to determine whether ATV pretreatment could attenuate myocardial apoptosis and inflammation and improve cardiac function in a swine model of coronary microembolization (CME). Methods: Twenty-four swine were randomly and equally divided into a sham-operated (control) group, CME group, and CME plus ATV group. Swine CME was induced by intracoronary injection of inert plastic microspheres (diameter 42 μm) into the left anterior descending coronary, with or without pretreatment of ATV. Echocardiographic measurements, a pathological examination, terminal deoxynucleotidyl transferase–mediated nick end labeling staining, and Western blotting were performed to assess the functional, morphological, and molecular effects in CME. Results: The expression levels of caspase 3 and tumor necrosis factor-α (TNF-α) were aberrantly upregulated in cardiomyocytes following CME. Downregulation of caspase 3 and TNF-α with ATV pretreatment was associated with improved cardiac function and attenuated serum cardiac troponin I (cTnI) and high-sensitivity C-reactive protein. In addition, through a Pearson correlation analysis, the left ventricular ejection fraction negatively correlated with caspase 3, TNF-α, and cTnI. Conclusion: This study demonstrated that ATV pretreatment could significantly inhibit CME-induced myocardial apoptosis and inflammation and improve cardiac function. The data generated from this study provide a rationale for the development of myocardial apoptosis and inflammation-based therapeutic strategies for CME-induced myocardial injury.

scholarly journals Levosimendan Protects against Doxorubicin-Induced Cardiotoxicity by Regulating the PTEN/Akt Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Ling-Li Li ◽  
Li Wei ◽  
Ning Zhang ◽  
Wen-Ying Wei ◽  
Can Hu ◽  
...  
Keyword(s):  
Critical Role ◽  
Cardiac Injury ◽  
Protective Role ◽  
Akt Inhibitor ◽  
Morphological Examination ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Myocardial Apoptosis

Background and Aims. Myocyte apoptosis plays a critical role in the development of doxorubicin- (DOX-) induced cardiotoxicity. In addition to its cardiotonic effect, laboratory evidence indicates that levosimendan can inhibit apoptosis, but its role in DOX-induced cardiac injury remains unclear. Therefore, the present study is aimed at exploring whether levosimendan could attenuate DOX-induced cardiotoxicity. Methods. Levosimendan (1 mg/kg) was administered to mice through oral gavage once daily for 4 weeks, and the mice were also subjected to an intraperitoneal injection of DOX (5 mg/kg) or saline, once a week for 4 weeks, to create a chronic model of DOX-induced cardiotoxicity. A morphological examination and biochemical analysis were used to evaluate the effects of levosimendan. H9C2 cells were used to verify the protective role of levosimendan in vitro. And an Akt inhibitor was utilized to verify the cardioprotection of levosimendan. Results. Levosimendan reduced the cardiac dysfunction and attenuated the myocardial apoptosis induced by DOX in vivo and in vitro. Levosimendan also inhibited the activation of phosphatase and tensin homolog (PTEN) and upregulated P-Akt expression both in vivo and in vitro. And inhibition of Akt abolished the cardioprotection of levosimendan in vitro. Conclusion. Levosimendan may protect against DOX-induced cardiotoxicity via modulation of the PTEN/Akt signaling pathway.

scholarly journals Rosuvastatin protects against coronary microembolization-induced cardiac injury via inhibiting NLRP3 inflammasome activation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ao Chen ◽  
Zhangwei Chen ◽  
You Zhou ◽  
Yuan Wu ◽  
Yan Xia ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Cardiac Injury ◽  
Serum Lactate Dehydrogenase ◽  
Inflammasome Activation ◽  
H9c2 Cells ◽  
Iodide Uptake ◽  
Coronary Microembolization ◽  
Mitochondrial Ros

AbstractCoronary microembolization (CME), a common reason for periprocedural myocardial infarction (PMI), bears very important prognostic implications. However, the molecular mechanisms related to CME remain largely elusive. Statins have been shown to prevent PMI, but the underlying mechanism has not been identified. Here, we examine whether the NLRP3 inflammasome contributes to CME-induced cardiac injury and investigate the effects of statin therapy on CME. In vivo study, mice with CME were treated with 40 mg/kg/d rosuvastatin (RVS) orally or a selective NLRP3 inflammasome inhibitor MCC950 intraperitoneally (20 mg/kg/d). Mice treated with MCC950 and RVS showed improved cardiac contractile function and morphological changes, diminished fibrosis and microinfarct size, and reduced serum lactate dehydrogenase (LDH) level. Mechanistically, RVS decreased the expression of NLRP3, caspase-1, interleukin-1β, and Gasdermin D N-terminal domains. Proteomics analysis revealed that RVS restored the energy metabolism and oxidative phosphorylation in CME. Furthermore, reduced reactive oxygen species (ROS) level and alleviated mitochondrial damage were observed in RVS-treated mice. In vitro study, RVS inhibited the activation of NLRP3 inflammasome induced by tumor necrosis factor α plus hypoxia in H9c2 cells. Meanwhile, the pyroptosis was also suppressed by RVS, indicated by the increased cell viability, decreased LDH and propidium iodide uptake in H9c2 cells. RVS also reduced the level of mitochondrial ROS generation in vitro. Our results indicate the NLRP3 inflammasome-dependent cardiac pyroptosis plays an important role in CME-induced cardiac injury and its inhibitor exerts cardioprotective effect following CME. We also uncover the anti-pyroptosis role of RVS in CME, which is associated with regulating mitochondrial ROS.

scholarly journals Activation of Nrf2 by miR-152 Inhibits Doxorubicin-Induced Cardiotoxicity via Attenuation of Oxidative Stress, Inflammation, and Apoptosis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Wen-Bin Zhang ◽  
Xin Lai ◽  
Xu-Feng Guo
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Viral Vector ◽  
Cardiac Injury ◽  
Cell Loss ◽  
Nuclear Factor ◽  
Protective Effects ◽  
Myocardial Apoptosis ◽  
Promising Therapeutic Target ◽  
Nrf2 Signaling Pathway

Doxorubicin (DOX) could trigger congestive heart failure, which largely limited the clinical use of DOX. microRNAs (miRNAs) were closely involved in the pathogenesis of DOX-induced cardiomyopathy. Here, we aimed to investigate the effect of miR-152 on DOX-induced cardiotoxicity in mice. To study this, we used an adeno-associated viral vector to overexpress miR-152 in mice 6 weeks before DOX treatment, using a dose mimicking the concentrations used in the clinics. In response to DOX injection, miR-152 was significantly decreased in murine hearts and cardiomyocytes. After DOX treatment, mice with miR-152 overexpression in the hearts developed less cardiac dysfunction, oxidative stress, inflammation, and myocardial apoptosis. Furthermore, we found that miR-152 overexpression attenuated DOX-related oxidative stress, inflammation, and cell loss in cardiomyocytes, whereas miR-152 knockdown resulted in oxidative stress, inflammation, and cell loss in cardiomyocytes. Mechanistically, this effect of miR-152 was dependent on the activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in response to DOX. Notably, Nrf2 deficiency blocked the protective effects of miR-152 against DOX-related cardiac injury in mice. In conclusion, miR-152 protected against DOX-induced cardiotoxicity via the activation of the Nrf2 signaling pathway. These results suggest that miR-152 may be a promising therapeutic target for the treatment of DOX-induced cardiotoxicity.

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