Nobiletin protects against myocardial injury and myocardial apoptosis following coronary microembolization via activating PI3K/Akt pathway in rats

2019 ◽  
Vol 392 (9) ◽  
pp. 1121-1130 ◽  
Author(s):  
Qing Mao ◽  
Xiulin Liang ◽  
Yufu Wu ◽  
Yongxiang Lu
Keyword(s):  
Myocardial Injury ◽  
Akt Pathway ◽  
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.

Aloperine Activates the PI3K/Akt Pathway and Protects Against Coronary Microembolisation-Induced Myocardial Injury in Rats

Pharmacology ◽  
2019 ◽  
Vol 104 (1-2) ◽  
pp. 90-97 ◽  
Author(s):  
Qing Mao ◽  
Fenfen Guo ◽  
Xiulin Liang ◽  
Yufu Wu ◽  
Yongxiang Lu
Keyword(s):  
Cardiac Dysfunction ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Troponin I ◽  
Serum Levels ◽  
Protective Role ◽  
Akt Pathway ◽  
Sprague Dawley ◽  
Myocardial Apoptosis ◽  
Phosphorylated Akt

Background: Coronary microembolisation (CME)-induced myocardial apoptosis is a key factor in progressive cardiac dysfunction. Aloperine (ALO) plays a protective role in the cardiovascular system, but its role and the mechanism ­underlying its protection against CME are unclear. Therefore, we aimed to verify whether ALO has a protective effect against CME-induced myocardial injury, as well as whether this effect has a relationship with regulation of the PI3K/Akt pathway for rats. Methods: Forty Sprague-Dawley rats were randomised into 4 equal groups: CME, CME + ALO, CME + ALO + LY294002 (LY) and a Sham group. Twelve hours after surgery, the rats’ cardiac function, apoptosis index, microinfarct and serum cardiac-troponin I (cTnI) level were measured. Levels of p-Akt, total Akt, Bcl-2, Bax and cleaved caspase-3 were detected. Results: ALO improved cardiac dysfunction induced by CME, while also decreasing serum levels of cTnI and microinfarct areas. In addition, ALO inhibited myocardial apoptosis, which may have been partially as a result of downregulated cleaved caspase-3 and Bax, upregulated Bcl-2 and increased protein levels in phosphorylated Akt. However, these ALO effects were blocked if ALO was administered along with LY. Conclusions: ALO can inhibit cardiomyocyte apoptosis and consequently attenuate CME-induced myocardial injury. These functions are realised by activating PI3K/Akt signalling pathway.

scholarly journals TAK-242 Protects Against Apoptosis in Coronary Microembolization-Induced Myocardial Injury in Rats by Suppressing TLR4/NF-κB Signaling Pathway

2017 ◽  
Vol 41 (4) ◽  
pp. 1675-1683 ◽  
Author(s):  
Xian-tao Wang ◽  
Yuan-xi Lu ◽  
Yu-han Sun ◽  
Wen-kai He ◽  
Jia-bao Liang ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Signaling Pathway ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Sham Group ◽  
Left Ventricular ◽  
Apoptotic Index ◽  
Tunel Staining ◽  
Coronary Microembolization ◽  
Myocardial Apoptosis

Background/Aims: Myocardial apoptosis is heavily implicated in the myocardial injury caused by coronary microembolization (CME), and toll-like receptor 4 (TLR4) is considered to be involved in this apoptotic cascade. Therefore, the present study was designed to investigate the role of TLR4/NF-κB signaling pathway regulated by TAK-242, a selective TLR4 signal transduction inhibitor, in the myocardial apoptosis after CME in rats. Methods: Forty-five rats were randomized (random number) into three groups: sham, CME and CME + TAK-242 (n = 15 per group).CME was induced by injecting polyethylene microspheres (42µm) into the left ventricular except the sham group. CME + TAK-242 group was treated with TAK-242 (2mg/kg) via the tail vein 30 minutes before CME modeling. Cardiac function was evaluated 6 hours after operation. Tissue biopsy was stained with HBFP to measure the size of micro-infarction area. TUNEL staining was used to detect myocardial apoptosis. Western blot and qPCR were used to evaluate the expression of TLR4, MyD88, NF-κB p65, p-IκBα and Cleaved caspase-3. Results: Cardiac function in the CME group and CME + TAK-242 group were significantly decreased compared with the sham group (P < 0.05) and the micro-infarction area, the apoptotic index, the expression of TLR4, NF-κB p65, p-IκBα and Cleaved caspase-3 were increased significantly (P < 0.05). Cardiac function in the CME + TAK-242 group was significantly improved compared with the CME group (P < 0.05) and the micro-infarction area, the apoptotic index, the expression of TLR4, MyD88, NF-κB p65, p-IκBα and Cleaved caspase-3 were decreased significantly (P < 0.05). Conclusions: TAK-242 can effectively improve CME-induced cardiac dysfunction by regulating TLR4/NF-κB signaling pathway and then reducing the myocardial apoptosis.

Protective effects and mechanism of curcumin on myocardial injury induced by coronary microembolization

2018 ◽  
Vol 120 (4) ◽  
pp. 5695-5703 ◽  
Author(s):  
Yang Liu ◽  
Yuanhang Liu ◽  
Xuecheng Huang ◽  
Jingchang Zhang ◽  
Lihui Yang
Keyword(s):  
Myocardial Injury ◽  
Protective Effects ◽  
Coronary Microembolization

scholarly journals Overexpression of lncRNA TUG1 Alleviates NLRP3 Inflammasome-Mediated Cardiomyocyte Pyroptosis Through Targeting the miR-186-5p/XIAP Axis in Coronary Microembolization-Induced Myocardial Damage

2021 ◽  
Vol 12 ◽  
Author(s):  
You Zhou ◽  
Tao Li ◽  
Zhiqing Chen ◽  
Junwen Huang ◽  
Zhenbai Qin ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Myocardial Injury ◽  
Culture Supernatant ◽  
Myocardial Damage ◽  
Luciferase Reporter ◽  
Cell Culture Supernatant ◽  
Coronary Microembolization ◽  
Lncrna Tug1

Coronary microembolization (CME) is a complicated problem that commonly arises in the context of coronary angioplasty. The lncRNA taurine-up regulated gene 1 (TUG1), significantly contributes to cardiovascular diseases; however, its contribution to CME-induced myocardial damage remains elusive. Herein, we establish the rat CME model and investigate the role of TUG1 in CME. The cell viability was evaluated via CCK-8 assay. Serum and cell culture supernatant samples were evaluated via ELISA. The dual luciferase reporter (DLR) assay, RIP, and RNA-pull down were conducted to validate the associations between TUG1 and miR-186-5p as well as miR-186-5p and XIAP. The expression of TUG1, miR-186-5p, and XIAP mRNA were determined by RT-qPCR, and proteins were evaluated via immuneblotting. As a result, TUG1 and XIAP were significantly down-regulated, and the miR-186-5p level was found to be remarkably up-regulated in CME myocardial tissues. Overexpression of TUG1 alleviated CME-induced myocardial injury and pyroptosis, whereas TUG1 knockdown showed the opposite effects. The DLR assay, RIP, and RNA-pull down results reveal that TUG1 directly targets miR-186-5p and miR-186-5p directly targets XIAP. In vitro rescue experiments show that TUG1 overexpression alleviates LPS-caused cardiomyocyte injury and pyroptosis via sponging miR-186-5p and regulating XIAP, and depression of miR-186-5p reduces LPS-induced cardiomyocyte injury and pyroptosis by targeting XIAP. Concludingly, the overexpression of TUG1 alleviates NLRP3 inflammasome-mediated cardiomyocyte pyroptosis through targeting the miR-186-5p/XIAP axis in CME-induced myocardial injury.

scholarly journals Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury

2018 ◽  
Vol 47 (4) ◽  
pp. 1497-1508 ◽  
Author(s):  
Qiang Su ◽  
Lang Li ◽  
Yuhan Sun ◽  
Huafeng Yang ◽  
Ziliang Ye ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Cardiac Function ◽  
Nlrp3 Inflammasome ◽  
Myocardial Injury ◽  
Neonatal Rat ◽  
Myocardial Inflammation ◽  
Inflammasome Activation ◽  
Coronary Microembolization ◽  
Coronary Syndrome ◽  
Nlrp3 Inflammasome Activation

Background/Aims: Coronary microembolization (CME) is a common complication of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI); Myocardial inflammation, caused by CME, is the main cause of cardiac injury. TLR4/MyD88/NF-κB signaling plays an important role in the development of myocardial inflammation, but its effects on CME remain unclear. To assess the cardiac protective effects of TAK-242 (TLR4 specific inhibitor) on CME-induced myocardial injury, and explore the underlying mechanism. Methods: Cardiac function, serum c-troponin I level, microinfarct were examined by cardiac ultrasound, myocardial enzyme assessment, HBFP staining. The levels of TLR4/MyD88/NF-κB signaling and NLRP3 inflammasome pathway were detected by ELISA, qRT-PCR and western blot. Results: The results showed inflammatory responses in the myocardium after CME, with increased expression levels of pro-inflammatory factors TNF-α, IL-1β and IL-18. Meanwhile, TLR4/MyD88/NF-κB signaling and the NLRP3 inflammasome were involved in the inflammatory process. TAK-242 administration before CME effectively inhibited the inflammatory response in the rat myocardium after CME and reduced myocardial injury, mainly by inhibiting TLR4/ MyD88/NF-κB signaling and reducing NLRP3 inflammasome activation. In addition, in vitro assays with neonatal rat cardiomyocytes further confirmed that TLR4/MyD88/NF-κB signaling was significantly activated in the inflammatory response of LPS-induced cardiomyocytes, via activation of the NLRP3 inflammasome. Inhibition of TLR4/MyD88/NF-κB signaling resulted in increased survival of cardiomyocytes mainly by reducing the release of inflammatory cytokines and decreasing NLRP3 inflammasome activation. Conclusions: TLR4/MyD88/NF-κB signaling participates in the inflammatory response of the myocardium after CME, activating the NLRP3 inflammasome, promoting the inflammatory cascade, and aggravating myocardial injury. Blocking TLR4/MyD88/NF-κB signaling may help reduce myocardial injury and improve cardiac function after CME.

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