Postconditioning with rosuvastatin reduces myocardial ischemia-reperfusion injury by inhibiting high mobility group box 1 protein expression

Du, Xianjin; Hu, Xiaorong; Wei, Jie

doi:10.3892/etm.2013.1362

Cited by 12 publications

(14 citation statements)

References 21 publications

(27 reference statements)

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“…These results indicated that simvastatin may exert a cardioprotective effect by decreasing the myocardial expression of HMGB1, which may be associated with the myocardial ischemia-induced inhibition of ROS. This conclusion was consistent with the results of a recent study ( 27 ).…”

Section: Discussionsupporting

confidence: 94%

Postconditioning with simvastatin decreases myocardial injury in rats following acute myocardial ischemia

Yao

Yang

Han

et al. 2015

Experimental and Therapeutic Medicine

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The aim of the present study was to investigate whether postconditioning with simvastatin attenuated myocardial ischemia reperfusion injury by inhibiting the expression of high mobility group box 1 (HMGB1) in rat myocardium following acute myocardial ischemia. In total, 30 male Sprague-Dawley rats were divided into sham operation (sham; n=10), acute myocardial infarction (AMI; n=10) and simvastatin (sim; n=10) groups. The AMI and sim groups were subjected to ischemia for 30 min, followed by reperfusion for 180 min. The rats in the sim group were administered 20 mg/kg simvastatin intravenously 5 min prior to reperfusion. Subsequently, the infarct size, serum cardiac troponin (c-TnI), tumor necrosis factor (TNF)-α and myocardial malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity were measured. Western blot analysis was used to detect the protein expression of HMGB1. Postconditioning with simvastatin was shown to decrease the infarct size and HMGB1 expression levels in the myocardium following AMI (P<0.05). In addition, postconditioning with simvastatin not only decreased the serum levels of c-TnI and TNF-α (P<0.05), but also inhibited the increase in MDA levels and the reduction in SOD activity (P<0.05). Therefore, postconditioning with simvastatin was shown to attenuate myocardial injury. The underlying mechanism may be associated with the downregulation of HMGB1 expression in the ischemic myocardium.

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Section: Discussionsupporting

confidence: 94%

Postconditioning with simvastatin decreases myocardial injury in rats following acute myocardial ischemia

Yao

Yang

Han

et al. 2015

Experimental and Therapeutic Medicine

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“…HMGB1 can activate inflammatory pathways when released from dying cells ( 14 ). In the heart, pre- and post-conditioning with rosuvastatin has been shown to reduce ischemia/reperfusion myocardial injury through the inhibition of HMGB1 ( 29 , 30 ). Therefore, the present study aimed to investigate the effects of rosuvastatin in ADR-treated rats.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Kim et al ( 35 ) showed that rosuvastatin prevented the long-term detrimental effects of ADR on left ventricular function. Ke et al ( 30 ) and Du et al ( 29 ) showed that pre- and post-conditioning with rosuvastatin reduces ischemia/reperfusion myocardial injury through the inhibition of HMGB1. However, the direct effects of rosuvastatin on cardiac function were not observed in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, HMGB1 binding to RAGE results in anti-inflammatory cytokines, including IL-4 and IL-10, being upregulated following inflammatory injury ( 40 , 46 , 47 ). Du et al ( 29 ) showed that post-conditioning with rosuvastatin decreased markers of oxidative stress in rats following ischemia/reperfusion injury. In addition, Ke et al ( 30 ) showed that preconditioning with rosuvastatin decreased ischemia/reperfusion injury by reducing the accumulation of inflammatory cells and regulatory T cells in the heart, which is associated with increased production of inflammatory cytokines, including TNF-α and IFN-γ, and dysregulated anti-inflammatory cytokines, including IL-4 and IL-10 ( 48 ).…”

Section: Discussionmentioning

confidence: 99%

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Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats

et al. 2018

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Rosuvastatin has cardiac protective effects through its anti-inflammatory effects. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. The present study aimed to investigate the effects of rosuvastatin in adriamycin (ADR)-treated rats. Adult male rats were randomized to three groups: i) Control group, ii) ADR group, and iii) ADR+rosuvastatin group. Serum biochemical indices were measured using an enzyme-linked immunosorbent assay. Cardiac function was assessed by echocardiography. The expression of HMGB1 and receptors for advanced glycation end products (RAGE) were assessed by reverse transcription-quantitative polymerase chain reaction analysis, western blot analysis, and immunohistochemistry. Cytokines were measured using flow cytometry. Rosuvastatin improved the biochemical indices and cardiac morphology and alleviated the pathological lesions. In the ADR+rosuvastatin group, the mRNA and protein levels of HMGB1 and RAGE in the myocardium were significantly lower compared with those in the ADR group (both P<0.05). The results showed that rosuvastatin significantly reduced the levels of HMGB1 and RAGE in the myocardium of the ADR-treated rats. These results suggest that the protective effects of rosuvastatin may be associated with attenuation of the HMGB1/RAGE-mediated inflammatory response in ADR-treated rats. Despite this protective effect of rosuvastatin in the present study, it did not improve cardiac function in terms of the diastolic left ventricular internal dimension, systolic left ventricular internal dimension, left ventricular ejection fraction and left ventricular fractional shortening; this may be due the observation duration being insufficient.

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“…Treatment with HMGB1-neutralizing antibody remarkably ameliorates hepatic, kidney, and brain infarction (Levy et al, 2007; Liu et al, 2007c; Muhammad et al, 2008; Tsung et al, 2005; Watanabe et al, 2005; Wu et al, 2007). Like ischemic preconditioning, pretreatment of mice with HMGB1 can decrease I/R injury (Du et al, 2014; Izuishi et al, 2006; Wu et al, 2013b) and promote tissue regeneration (Biscetti et al, 2011). The protection observed in mice pretreated with HMGB1 partly depends on expression of IL-1R-associated kinase-M, a negative regulator of TLR4 signaling (Izuishi et al, 2006).…”

Section: Hmgb1 and Diseasementioning

confidence: 99%

HMGB1 in health and disease

Kang

Chen

Zhang

et al. 2014

Molecular Aspects of Medicine

798

828

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Complex genetic and physiological variations as well as environmental factors that drive emergence of chromosomal instability, development of unscheduled cell death, skewed differentiation, and altered metabolism are central to the pathogenesis of human diseases and disorders. Understanding the molecular bases for these processes is important for the development of new diagnostic biomarkers, and for identifying new therapeutic targets. In 1973, a group of non-histone nuclear proteins with high electrophoretic mobility was discovered and termed High-Mobility Group (HMG) proteins. The HMG proteins include three superfamilies termed HMGB, HMGN, and HMGA. High-mobility group box 1 (HMGB1), the most abundant and well-studied HMG protein, senses and coordinates the cellular stress response and plays a critical role not only inside of the cell as a DNA chaperone, chromosome guardian, autophagy sustainer, and protector from apoptotic cell death, but also outside the cell as the prototypic damage associated molecular pattern molecule (DAMP). This DAMP, in conjunction with other factors, thus has cytokine, chemokine, and growth factor activity, orchestrating the inflammatory and immune response. All of these characteristics make HMGB1 a critical molecular target in multiple human diseases including infectious diseases, ischemia, immune disorders, neurodegenerative diseases, metabolic disorders, and cancer. Indeed, a number of emergent strategies have been used to inhibit HMGB1 expression, release, and activity in vitro and in vivo. These include antibodies, peptide inhbitiors, RNAi, anti-coagulants, endogenous hormones, various chemical compounds, HMGB1-receptor and signaling pathway inhibition, artificial DNAs, physical strategies including vagus nerve stimulation and other surgical approaches. Future work further investigating the details of HMGB1 localizationtion, structure, post-translational modification, and identifccation of additional partners will undoubtedly uncover additional secrets regarding HMGB1’s multiple functions.

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Postconditioning with rosuvastatin reduces myocardial ischemia-reperfusion injury by inhibiting high mobility group box 1 protein expression

Cited by 12 publications

References 21 publications

Postconditioning with simvastatin decreases myocardial injury in rats following acute myocardial ischemia

Postconditioning with simvastatin decreases myocardial injury in rats following acute myocardial ischemia

Rosuvastatin reduces the pro-inflammatory effects of adriamycin on the expression of HMGB1 and RAGE in rats

HMGB1 in health and disease

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