S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE-dependent NF-kB signaling

Volz, Christian; Wienbrandt, AR; Katus, HA; Lasitschka, Felix; Andrassy, Martin

doi:10.1055/s-0032-1314767

Cited by 13 publications

(20 citation statements)

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“…In male rats, the half-life of U50,488H is only about 2 hours [24], while long-term benefits were observed up to 4 weeks post-ischemia in our animal model of MI/R. One possible mechanism by which U50,488H produces long-term protection against MI/R injury is through a reduction in cardiomyocyte death during the acute phase of reperfusion [4,25,26]. On the other hand, long-term effects may be independent of agonist presence.…”

Section: Discussionmentioning

confidence: 84%

Kappa-Opioid Agonist U50,488H-Mediated Protection Against Heart Failure Following Myocardial Ischemia/Reperfusion: Dual Roles of Heme Oxygenase-1

Tong

Zhang²,

Zhou³

et al. 2016

Cell Physiol Biochem

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Backgrounds/Aims: The selective κ-opioid agonist U50,488H protects heart from myocardial ischemia-reperfusion (MI/R) injury. We examined whether U50,488H is also beneficial for MI/R induced heart failure. Methods: Anesthetized male Sprague-Dawley rats were subjected to 30 min of myocardial ischemia via left anterior descending coronary artery (LAD) occlusion, followed by 4 weeks of reperfusion. Infarct size was examined by Evans blue/triphenyl tetrazolium chloride (TTC) staining. Cardiac function and remodeling were examined by echocardiography and histology. HO-1 gene transcription and expression were measured by RT-PCR and western blot. Results: Compared to vehicle-treated MI/R rats, rats administered a single dose of U50,488H at the beginning of reperfusion exhibited reduced myocardial infarct size, oxidative stress, hypertrophy, and fibrosis, improved mechanical function, and greater neovascularization. U50,488H also increased myocardial heme oxygenase (HO)-1 gene transcription and expression, while pharmacological HO-1 inhibition reversed all protective effects of U50,488H. Furthermore, U50,488H protected control cultured cardiomyoctes against simulated I/R-induced apoptosis but not cultures subjected to shRNA-mediated HO-1 knockdown. Inhibition of HO-1 in the subacute phase of reperfusion reversed the U50,488H-induced increase in neovascularization and suppression of oxidative stress. Finally, U50,488H increased Akt phosphorylation and nuclear translocation of Nrf2, a key HO-1 transcription activator, while inhibition of PI3K-Akt signaling abolished U50,488H-induced Nrf2 nuclear translocation, HO-1 upregulation, and cardioprotection. Conclusion: Activation of HO-1 expression through the PI3K-Akt-Nrf2 pathway may mediate the acute and long-term protective effects of U50,488H against heart failure by enhancing cardiomyocyte survival and neoangiogenesis and by reducing oxidative stress.

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Section: Discussionmentioning

confidence: 84%

Kappa-Opioid Agonist U50,488H-Mediated Protection Against Heart Failure Following Myocardial Ischemia/Reperfusion: Dual Roles of Heme Oxygenase-1

Tong

Zhang²,

Zhou³

et al. 2016

Cell Physiol Biochem

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“…CP was originally described as a protein constitutively expressed in the cytosol DOI: 10.3109/19396368.2014.949905 of neutrophils, mononuclear phagocytes, and keratinocytes. Subsequent studies recognized CP in several other cell types of inflamed tissues and in tumor cells [Ehrchen et al 2009;Gebhardt et al 2006;Striz and Trebichavsky 2004;Volz et al 2012]. Elevated CP levels in tissues and body fluids are considered a hallmark of pathological conditions associated with inflammation (e.g., rheumatoid arthritis, systemic lupus erythematosus, chronic inflammatory bowel diseases, cardiac diseases) [Ehrchen et al 2009;Gebhardt et al 2006;Striz and Trebichavsky 2004;Volz et al 2012].…”

Section: Discussionmentioning

confidence: 99%

“…Engagement of RAGE triggers several signaling molecules, including the transcription factor NF-kB, MAP kinases, and adhesion molecules, that stimulate the inflammatory responses and increase the oxidative stress [Bierhaus et al 2005;Ramasamy et al 2009;Yan et al 2009], with possible alteration of the testicular functions. There is evidence that CP is a RAGE ligand [Ehlermann et al 2006;Gebhardt et al 2006;Ghavami et al 2008;Ichikawa et al 2011;Leclerc et al 2009;Volz et al 2012], and that RAGE is activated and up-regulated by the presence of its own ligands [Clynes et al 2007;Gebhardt et al 2008;Ramasamy et al 2011;Schmidt et al 2009;Yan et al 2009]. Therefore, contemporary expression of CP and RAGE in the testicular tissues likely generates a positive feed back loop resulting in high inflammation levels.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, contemporary expression of CP and RAGE in the testicular tissues likely generates a positive feed back loop resulting in high inflammation levels. Upregulation of RAGE, as a consequence of RAGE-ligand interaction, was associated with various diseases, including diabetes, vascular diseases, neurodegenerative diseases, and cancer [Clynes et al 2007;Gebhardt et al 2008;Ichikawa et al 2011;Ramasamy et al 2011;Schmidt et al 2009;Volz et al 2012;Yan et al 2009]. Taken together, these observations allow one to suppose that the expression of CP and RAGE play a significant role in the alterations of the semen parameters occurring in chronic alcoholism [Condorelli et al 2014].…”

Section: Discussionmentioning

confidence: 99%

“…Recruitment of RAGE activates various cellular processes including inflammation and apoptosis [Bierhaus et al 2005;Ramasamy et al 2009;Yan et al 2009]. There is evidence that CP is a RAGE ligand and that CP and RAGE are frequently co-expressed in pathological tissues [Ehlermann et al 2006;Gebhardt et al 2006;Ghavami et al 2008;Ichikawa et al 2011;Leclerc et al 2009;Volz et al 2012]. The aim of our study was to determine whether CP and RAGE are expressed in testis of male mice subjected to chronic alcohol administration.…”

Section: Introductionmentioning

confidence: 96%

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Chronic alcohol administration causes expression of calprotectin and RAGE altering the distribution of zinc ions in mouse testis

Giannessi

Scavuzzo

Giambelluca

et al. 2014

Systems Biology in Reproductive Medicine

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Several studies reported that chronic alcohol consumption alters the intestinal mucosa barrier, and subsequent entrance of endotoxins into the bloodstream. In many tissues endotoxin exposure causes the expression of calprotectin (CP) and the receptor for advanced glycation -end products (RAGE). In this study we investigated whether chronic alcohol administration causes expression of CP and RAGE in mouse testis. The distribution of free and loosely bound Zn 2+ ) in the testicular tissues was also evaluated. Alcohol-induced testicular damage was documented by measuring testosterone blood levels and by light and electron microscope studies. Twenty mice were treated daily for three weeks with 3.0 g/kg of a 25% solution of alcohol. Ten mice were treated in the same period of time with a solution of maltose dextrins, isocaloric to alcohol. Twenty untreated mice were used as controls. Alcohol treated mice showed diffuse expression of CP and RAGE in the interstitial cells. RAGE was found also in the basal compartment of the seminiferous tubules. Depletion of FLB-Zn 2+ was observed in the adluminal compartment of the seminiferous tubules. Expression of CP and RAGE was not found in control mice and maltose dextrin treated mice. Our results indicated novel mechanisms by which alcohol acts in testis. Indeed, CP and RAGE may cause the generation of oxidants and inflammatory mediators, with negative impact on testicular functions. Depletion of FLB-Zn 2+ may contribute to the dysregulation of spermatogenesis.Abbreviations: CP: calprotectin; FLB-Zn 2+ : free and loosely bound Zn

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Association of rs2070600 in advanced glycosylation end‐product specific receptor with prognosis of heart failure

et al. 2020

ESC Heart Failure

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Aims Our objective was to investigate the association of common variants in the coding region of advanced glycosylation end-product specific receptor (RAGE) and the prognosis of heart failure (HF). Methods and results A total of 3394 HF patients were continuously enrolled from January 2009 to August 2018 with a median follow-up of 20.4 months. Additionally, 2861 healthy subjects also participated in the study. By sequencing these two groups, we identified a common functional missense variant rs2070600 in the coding region of RAGE, which showed a significant association with the prognosis of HF [hazard ratio = 0.53, 95%, confidence interval (CI) = 0.30-0.94, P = 0.03], but no association with the risk of HF (odds ratio = 0.52, 95%, CI = 0.66-1.04, P = 0.106). A series of functional assays revealed that rs2070600-A, but not-G allele, suppressed the expression of RAGE protein by facilitating the binding of miR-125a-3p. Furthermore, the RAGE messenger RNA levels of human peripheral blood lymphocytes were reduced in subjects with the rs2070600-AA genotype compared with subjects with the rs2070600-GG or-AG genotypes. Additionally, our Western blot results from human heart tissue showed increased RAGE expression in HF samples compared with that in healthy donors. Conclusions Our results demonstrate that the common missense variant rs2070600-A allele is associated with a reduced risk of cardiovascular death and cardiac transplantation by facilitating the binding of miR-125a-3p.

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S100A8/A9 aggravates post-ischemic heart failure through activation of RAGE-dependent NF-kB signaling

Cited by 13 publications

References 0 publications

Kappa-Opioid Agonist U50,488H-Mediated Protection Against Heart Failure Following Myocardial Ischemia/Reperfusion: Dual Roles of Heme Oxygenase-1

Kappa-Opioid Agonist U50,488H-Mediated Protection Against Heart Failure Following Myocardial Ischemia/Reperfusion: Dual Roles of Heme Oxygenase-1

Chronic alcohol administration causes expression of calprotectin and RAGE altering the distribution of zinc ions in mouse testis

Association of rs2070600 in advanced glycosylation end‐product specific receptor with prognosis of heart failure

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