High mobility group box 1 might be a novel therapeutic target in ischemia heart disease

Meng, Xiaoyan; Wu, Lei; Zhou, Yanhong; Liu, Tao; Han, Qian‐Feng; Zhang, Deyong; Wang, Lanhua; Yao, Heng‐Chen

doi:10.1016/j.ijcard.2016.01.014

Cited by 4 publications

(3 citation statements)

References 15 publications

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“…In addition, the application of anti-HMGB-1 antibody in hemorrhagic shock in mice was associated with decreased systemic release of cardiac enzymes, reduced local ATP depletion and systemic levels of inflammatory mediators like TNF and IL-1ß [25]. Extracellular HMGB-1 binds directly to TLR 4 as well as to the receptor for advanced glycation end products (RAGE), which was linked to the production and release of inflammatory cytokines [14,15] such as TNF, IL-1ß and IL-6 [16], which were shown to be cardio-depressive [26]. An increase of systemic IL-6 concentration has been linked to cardiac dysfunction, demonstrated as a reduction of stroke volume, cardiac output and the performance of the left ventricle [27,28].…”

Section: Discussionmentioning

confidence: 99%

“…In mice, the interaction between TLR 4 and HMGB-1 has been described in the development of liver injury [12]. Extracellular histones or HMGB-1 interaction with TLR4 increased the release of inflammatory cytokines such as tumor necrosis factor (TNF), interleukin (IL-)1ß and IL-6, which were shown to be cardio-depressive [13][14][15][16]. Additionally, histones were linked to the release of HMGB-1 via cell damage in liver, lung and kidney injuries in mice [13].…”

Section: Introductionmentioning

confidence: 99%

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Effects of Circulating HMGB-1 and Histones on Cardiomyocytes–Hemadsorption of These DAMPs as Therapeutic Strategy after Multiple Trauma

Weber

Lackner

Baur

et al. 2020

JCM

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Background and purpose: The aim of the study was to determine the effects of post-traumatically released High Mobility Group Box-1 protein (HMGB1) and extracellular histones on cardiomyocytes (CM). We also evaluated a therapeutic option to capture circulating histones after trauma, using a hemadsorption filter to treat CM dysfunction. Experimental Approach: We evaluated cell viability, calcium handling and mitochondrial respiration of human cardiomyocytes in the presence of HMGB-1 and extracellular histones. In a translational approach, a hemadsorption filter was applied to either directly eliminate extracellular histones or to remove them from blood samples obtained from multiple injured patients. Key results: Incubation of human CM with HMGB-1 or histones is associated with changes in calcium handling, a reduction of cell viability and a substantial reduction of the mitochondrial respiratory capacity. Filtrating plasma from injured patients with a hemadsorption filter reduces histone concentration ex vivo and in vitro, depending on dosage. Conclusion and implications: Danger associated molecular patterns such as HMGB-1 and extracellular histones impair human CM in vitro. A hemadsorption filter could be a therapeutic option to reduce high concentrations of histones.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of Circulating HMGB-1 and Histones on Cardiomyocytes–Hemadsorption of These DAMPs as Therapeutic Strategy after Multiple Trauma

Weber

Lackner

Baur

et al. 2020

JCM

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“…Systemic release of HMGB-1 after trauma correlated with the injury severity as well as with the mortality of the patients [19,52]. HMGB-1 was associated with the production of inflammatory cytokines like TNF, IL-1ß and IL-6 via Toll-like receptor-2,-4 and-9 [14,53,54]. Extracellular histones have been found to be cardio-depressive, leading to the development of posttraumatic as well as septic cardiomyopathy [55] Extracellular histones led dose-and time dependent to ROS production and increase of intracellular calcium, reduced dose-dependent the mitochondrial membrane potential and the ATP production, which resulted in reduced CM contraction, because of a lack of energy [56] [57].…”

Section: Plos Onementioning

confidence: 98%

Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing

et al. 2020

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Background Approximately 30,000 patients with blunt cardiac trauma are recorded each year in the United States. Blunt cardiac injuries after trauma are associated with a longer hospital stay and a poor overall outcome. Organ damage after trauma is linked to increased systemic release of pro-inflammatory cytokines and damage-associated molecular patterns. However, the interplay between polytrauma and local cardiac injury is unclear. Additionally, the impact of surgical intervention on this process is currently unknown. This study aimed to determine local cardiac immunological and structural alterations after multiple trauma. Furthermore, the impact of the chosen fracture stabilization strategy (reamed versus nonreamed femoral nailing) on cardiac alterations was studied. Experimental approach 15 male pigs were either exposed to multiple trauma (blunt chest trauma, laparotomy, liver laceration, femur fracture and haemorrhagic shock) or sham conditions. Blood samples as well as cardiac tissue were analysed 4 h and 6 h after trauma. Additionally, murine HL-1 cells were exposed to a defined polytrauma-cocktail, mimicking the pro-inflammatory conditions after multiple trauma in vitro. Results After multiple trauma, cardiac structural changes were observed in the left ventricle. More specifically, alterations in the alpha-actinin and desmin protein expression were found. Cardiac structural alterations were accompanied by enhanced local nitrosative stress, increased local inflammation and elevated systemic levels of the high-mobility group box 1

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Sodium‐Glucose Co‐Transporter‐2 Inhibitor Empagliflozin Attenuates Sorafenib‐Induced Myocardial Inflammation and Toxicity

Liu,

Ho,

Lee

et al. 2024

Environmental Toxicology

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Environmental antineoplastics such as sorafenib may pose a risk to humans through water recycling, and the increased risk of cardiotoxicity is a clinical issue in sorafenib users. Thus, developing strategies to prevent sorafenib cardiotoxicity is an urgent work. Empagliflozin, as a sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor for type 2 diabetes control, has been approved for heart failure therapy. Still, its cardioprotective effect in the experimental model of sorafenib cardiotoxicity has not yet been reported. Real‐time quantitative RT‐PCR (qRT‐PCR), immunoblot, and immunohistochemical analyses were applied to study the effect of sorafenib exposure on cardiac SGLT2 expression. The impact of empagliflozin on cell viability was investigated in the sorafenib‐treated cardiomyocytes using Alamar blue assay. Immunoblot analysis was employed to delineate the effect of sorafenib and empagliflozin on ferroptosis/proinflammatory signaling in cardiomyocytes. Ferroptosis/DNA damage/fibrosis/inflammation of myocardial tissues was studied in mice with a 28‐day sorafenib ± empagliflozin treatment using histological analyses. Sorafenib exposure significantly promoted SGLT2 upregulation in cardiomyocytes and mouse hearts. Empagliflozin treatment significantly attenuated the sorafenib‐induced cytotoxicity/DNA damage/fibrosis in cardiomyocytes and mouse hearts. Moreover, GPX4/xCT‐dependent ferroptosis as an inducer for releasing high mobility group box 1 (HMGB1) was also blocked by empagliflozin administration in the sorafenib‐treated cardiomyocytes and myocardial tissues. Furthermore, empagliflozin treatment significantly inhibited the sorafenib‐promoted NFκB/HMGB1 axis in cardiomyocytes and myocardial tissues, and sorafenib‐stimulated proinflammatory signaling (TNF‐α/IL‐1β/IL‐6) was repressed by empagliflozin administration. Finally, empagliflozin treatment significantly attenuated the sorafenib‐promoted macrophage recruitments in mouse hearts. In conclusion, empagliflozin may act as a cardioprotective agent for humans under sorafenib exposure by modulating ferroptosis/DNA damage/fibrosis/inflammation. However, further clinical evidence is required to support this preclinical finding.

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High mobility group box 1 might be a novel therapeutic target in ischemia heart disease

Cited by 4 publications

References 15 publications

Effects of Circulating HMGB-1 and Histones on Cardiomyocytes–Hemadsorption of These DAMPs as Therapeutic Strategy after Multiple Trauma

Effects of Circulating HMGB-1 and Histones on Cardiomyocytes–Hemadsorption of These DAMPs as Therapeutic Strategy after Multiple Trauma

Structural alterations and inflammation in the heart after multiple trauma followed by reamed versus non-reamed femoral nailing

Sodium‐Glucose Co‐Transporter‐2 Inhibitor Empagliflozin Attenuates Sorafenib‐Induced Myocardial Inflammation and Toxicity

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