Activation of the mammalian target of rapamycin signaling pathway underlies a novel inhibitory role of ring finger protein 182 in ventricular remodeling after myocardial ischemia‐reperfusion injury

2018 ◽  
Vol 120 (5) ◽  
pp. 7635-7648 ◽  
Author(s):  
Jing‐Hua Wang ◽  
Zhi‐Feng Wei ◽  
Yan‐Li Gao ◽  
Cong‐Cong Liu ◽  
Jing‐Hui Sun
Keyword(s):  
Ventricular Remodeling ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Ring Finger ◽  
Ring Finger Protein ◽  
Finger Protein ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Interleukin 35 protects cardiomyocytes following ischemia/reperfusion-induced apoptosis via activation of mitochondrial STAT3

2021 ◽  
Author(s):  
Fengyun Zhou ◽  
Ting Feng ◽  
Xiangqi Lu ◽  
Huicheng Wang ◽  
Yangping Chen ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Role ◽  
Cytochrome C Release ◽  
Neonatal Cardiomyocytes ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Abstract Mitochondrial reactive oxygen species (mtROS)-induced apoptosis has been suggested to contribute to myocardial ischemia/reperfusion injury. Interleukin 35 (IL-35), a novel anti-inflammatory cytokine, has been shown to protect the myocardium and inhibit mtROS production. However, its effect on cardiomyocytes upon exposure to hypoxia/reoxygenation (H/R) damage has not yet been elucidated. The present study aimed to investigate the potential protective role and underlying mechanisms of IL-35 in H/R-induced mouse neonatal cardiomyocyte injury. Mouse neonatal cardiomyocytes were challenged to H/R in the presence of IL-35, and we found that IL-35 dose dependently promotes cell viability, diminishes mtROS, maintains mitochondrial membrane potential, and decreases the number of apoptotic cardiomyocytes. Meanwhile, IL-35 remarkably activates mitochondrial STAT3 (mitoSTAT3) signaling, inhibits cytochrome c release, and reduces apoptosis signaling. Furthermore, co-treatment of the cardiomyocytes with the STAT3 inhibitor AG490 abrogates the IL-35-induced cardioprotective effects. Our study identified the protective role of IL-35 in cardiomyocytes following H/R damage and revealed that IL-35 protects cardiomyocytes against mtROS-induced apoptosis through the mitoSTAT3 signaling pathway during H/R.

MicroRNA-330-5p inhibits NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury by targeting TIM3

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Zuo ◽  
R Tian ◽  
Q Chen ◽  
L Wang ◽  
Q Gu ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Nlrp3 Inflammasome ◽  
Ischemia Reperfusion Injury ◽  
Infarct Volume ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Abstract Background Myocardial ischemia-reperfusion injury (MIRI) is one of the leading causes of human death. Nod-like receptor protein-3 (NLRP3) inflammasome signaling pathway involved in the pathogenesis of MIRI. However, the upstream regulating mechanisms of NLRP3 at molecular level remains unknown. Purpose This study investigated the role of microRNA330-5p (miR-330-5p) in NLRP3 inflammasome-mediated MIRI and the associated mechanism. Methods Mice underwent 45 min occlusion of the left anterior descending coronary artery followed by different times of reperfusion. Myocardial miR-330-5p expression was examined by quantitative polymerase chain reaction (PCR), and miR-330-5p antagomir and agomir were used to regulate miR-330-5p expression. To evaluate the role of miR-330-5p in MIRI, Evans Blue (EB)/2, 3, 5-triphenyltetrazolium chloride (TTC) staining, echocardiography, and immunoblotting were used to assess infarct volume, cardiac function, and NLRP3 inflammasome activation, respectively. Further, in vitro myocardial ischemia-reperfusion model was established in cardiomyocytes (H9C2 cell line). A luciferase binding assay was used to examine whether miR-330-5p directly bound to T-cell immunoglobulin domain and mucin domain-containing molecule-3 (TIM3). Finally, the role of miR-330-5p/TIM3 axis in regulating apoptosis and NLRP3 inflammasome formation were evaluated using flow cytometry assay and immunofluorescence staining. Results Compared to the model group, inhibiting miR-330-5p significantly aggravated MIRI resulting in increased infarct volume (58.09±6.39% vs. 37.82±8.86%, P<0.01) and more severe cardiac dysfunction (left ventricular ejection fraction [LVEF] 12.77%±6.07% vs. 27.44%±4.47%, P<0.01; left ventricular end-diastolic volume [LVEDV] 147.18±25.82 vs. 101.31±33.20, P<0.05; left ventricular end-systolic volume [LVESV] 129.11±30.17 vs. 74.29±28.54, P<0.05). Moreover, inhibiting miR-330-5p significantly increased the levels of NLRP3 inflammasome related proteins including caspase-1 (0.80±0.083 vs. 0.60±0.062, P<0.05), interleukin (IL)-1β (0.87±0.053 vs. 0.79±0.083, P<0.05), IL-18 (0.52±0.063 vs. 0.49±0.098, P<0.05) and tissue necrosis factor (TNF)-α (1.47±0.17 vs. 1.03±0.11, P<0.05). Furthermore, TIM3 was confirmed as a potential target of miR-330-5p. As predicted, suppression of TIM3 by small interfering RNA (siRNA) ameliorated the anti-miR-330-5p-mediated apoptosis of cardiomyocytes and activation of NLRP3 inflammasome signaling pathway (Figure 1). Conclusion Overall, our study indicated that miR-330-5p/TIM3 axis involved in the regulating mechanism of NLRP3 inflammasome-mediated myocardial ischemia-reperfusion injury. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): National Natural Science Foundation of China Grants

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