Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation
Using an experimental model of surgical deep hypothermic circulatory arrest (DHCA), we hypothesized that hibernating arctic ground squirrels (AGS) display reduced myocardial injury following I/R compared to a non-hibernator (rat) through reduced NF-kB signaling and myocardial inflammation. We furthe...
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2012
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Online Access: | http://dx.doi.org/10.1161/circ.126.suppl_21.a19524 |
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crovidcr:10.1161/circ.126.suppl_21.a19524 2024-09-09T19:27:26+00:00 Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation Podgoreanu, Mihai V Ma, Qing Zhang, Zhiquan Bain, James Newgard, Christopher B Riess, Matthias Barnes, Brian M 2012 http://dx.doi.org/10.1161/circ.126.suppl_21.a19524 en eng Ovid Technologies (Wolters Kluwer Health) Circulation volume 126, issue suppl_21 ISSN 0009-7322 1524-4539 journal-article 2012 crovidcr https://doi.org/10.1161/circ.126.suppl_21.a19524 2024-07-04T04:14:58Z Using an experimental model of surgical deep hypothermic circulatory arrest (DHCA), we hypothesized that hibernating arctic ground squirrels (AGS) display reduced myocardial injury following I/R compared to a non-hibernator (rat) through reduced NF-kB signaling and myocardial inflammation. We further explored the role of myocardial accumulation of ceramides, known regulators of NF-kB inflammatory signaling, in the hibernator cardioprotective phenotype. Methods: Euthermic AGS aroused from torpor and rats underwent DHCA (45min, with 3 or 24h reperfusion) or sham. We compared between species/time points by two-way ANOVA: 1) biochemical severity of myocardial injury (plasma HFABP, TnI, ELISA); 2) myocardial apoptosis (activated caspase-3, immunostaining; TUNEL); 3) myocardial NF-kB activation (transcription factor binding assay; nuclear translocation) 4) myocardial cytokine expression and leukocyte extravasation; 5) myocardial PPARa activity (ELISA); 6) myocardial levels of 12 ceramides (MS) Results: Compared to rats, AGS displayed robust ischemic tolerance following DHCA (Fig A). This was accompanied by reduced NF-kB DNA binding activity and nuclear translocation (Fig B), as well as decreased expression of downstream inflammatory cytokines. Significant post-I/R accumulation of 4 species of sphingoid base ceramides and 1 monohexosyl ceramide was found in rat vs AGS. Preservation of myocardial PPARa activity occurred in AGS, but was significantly downregulated in the rat (Fig B). Conclusion: We found an association between the hibernator cardioprotective phenotype and differences in myocardial activation of NF-kB inflammatory signaling. Mechanistically, this was associated with a) accumulation of several species of ceramides in rat vs AGS hearts, previously implicated in triggering mitochondrial dysfunction and apoptosis following I/R; and b) preservation of PPARa activity in AGS, with known dual metabolic anti-inflammatory effects. Article in Journal/Newspaper Arctic Ovid Arctic Circulation 126 suppl_21 |
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English |
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Using an experimental model of surgical deep hypothermic circulatory arrest (DHCA), we hypothesized that hibernating arctic ground squirrels (AGS) display reduced myocardial injury following I/R compared to a non-hibernator (rat) through reduced NF-kB signaling and myocardial inflammation. We further explored the role of myocardial accumulation of ceramides, known regulators of NF-kB inflammatory signaling, in the hibernator cardioprotective phenotype. Methods: Euthermic AGS aroused from torpor and rats underwent DHCA (45min, with 3 or 24h reperfusion) or sham. We compared between species/time points by two-way ANOVA: 1) biochemical severity of myocardial injury (plasma HFABP, TnI, ELISA); 2) myocardial apoptosis (activated caspase-3, immunostaining; TUNEL); 3) myocardial NF-kB activation (transcription factor binding assay; nuclear translocation) 4) myocardial cytokine expression and leukocyte extravasation; 5) myocardial PPARa activity (ELISA); 6) myocardial levels of 12 ceramides (MS) Results: Compared to rats, AGS displayed robust ischemic tolerance following DHCA (Fig A). This was accompanied by reduced NF-kB DNA binding activity and nuclear translocation (Fig B), as well as decreased expression of downstream inflammatory cytokines. Significant post-I/R accumulation of 4 species of sphingoid base ceramides and 1 monohexosyl ceramide was found in rat vs AGS. Preservation of myocardial PPARa activity occurred in AGS, but was significantly downregulated in the rat (Fig B). Conclusion: We found an association between the hibernator cardioprotective phenotype and differences in myocardial activation of NF-kB inflammatory signaling. Mechanistically, this was associated with a) accumulation of several species of ceramides in rat vs AGS hearts, previously implicated in triggering mitochondrial dysfunction and apoptosis following I/R; and b) preservation of PPARa activity in AGS, with known dual metabolic anti-inflammatory effects. |
format |
Article in Journal/Newspaper |
author |
Podgoreanu, Mihai V Ma, Qing Zhang, Zhiquan Bain, James Newgard, Christopher B Riess, Matthias Barnes, Brian M |
spellingShingle |
Podgoreanu, Mihai V Ma, Qing Zhang, Zhiquan Bain, James Newgard, Christopher B Riess, Matthias Barnes, Brian M Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation |
author_facet |
Podgoreanu, Mihai V Ma, Qing Zhang, Zhiquan Bain, James Newgard, Christopher B Riess, Matthias Barnes, Brian M |
author_sort |
Podgoreanu, Mihai V |
title |
Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation |
title_short |
Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation |
title_full |
Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation |
title_fullStr |
Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation |
title_full_unstemmed |
Abstract 19524: The Cardioprotective Phenotype in Mammalian Hibernators is Associated with Attenuation of Reperfusion-Induced Nuclear Factor-Kappa B Regulated Myocardial Inflammation |
title_sort |
abstract 19524: the cardioprotective phenotype in mammalian hibernators is associated with attenuation of reperfusion-induced nuclear factor-kappa b regulated myocardial inflammation |
publisher |
Ovid Technologies (Wolters Kluwer Health) |
publishDate |
2012 |
url |
http://dx.doi.org/10.1161/circ.126.suppl_21.a19524 |
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Arctic |
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Arctic |
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Arctic |
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Arctic |
op_source |
Circulation volume 126, issue suppl_21 ISSN 0009-7322 1524-4539 |
op_doi |
https://doi.org/10.1161/circ.126.suppl_21.a19524 |
container_title |
Circulation |
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126 |
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suppl_21 |
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1809896852626079744 |