Pressure overload promotes HMGB1 signaling in the ischemic-reperfused heart

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2 Citations (Scopus)

Abstract

Damage-Associated Molecular Patterns (DAMPs) are released following tissue injury and can activate pro-inflammatory pathways. Prototypical DAMPs include the High-Mobility Group Box 1 (HMGB1) protein which is released from necrotic cells. In turn, HMGB1 promotes inflammation via mechanisms likely involving phosphorylation/ activation of c-Jun-NH2-Terminal Kinase (JNK) and production of the inflammasome-associated cytokine, interleukin-1β (IL-1β). We have shown that pressure overload increases infarct size in association with poorer functional recovery of the heart subjected to an ischemia-reperfusion insult. This study tested the hypothesis that pressure overload augments HMGB1 expression in association with increased IL-1β generation and JNK phosphorylation thereby contributing to increased tissue injury. Accordingly, hearts of male Sprague-Dawley rats were subjected to an ischemia (40 min) reperfusion (15 min) insult with perfusion pressure set at either 80 or 160 cm H 2 O. Thereafter, hearts were processed for flow cytometry and Western blot studies. The ischemic-reperfused hearts subjected to the high pressure displayed (a) greater expression of HMGB1 and IL-1β which were shown to also be generated by cardiomyocytes, (b) increased phosphoJNK levels and c) increased necrotic and apoptotic cell death. Collectively, the results suggest that pressure-related upregulation of HMGB1 signaling contributes to the pro-inflammatory response of the ischemic-reperfused heart involving augmented JNK activation and IL-1β generation.

Original languageEnglish (US)
JournalJournal of Clinical and Experimental Cardiology
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2014

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Interleukin-1
JNK Mitogen-Activated Protein Kinases
Pressure
Reperfusion
Ischemia
Phosphorylation
Inflammasomes
HMGB1 Protein
Wounds and Injuries
Cardiac Myocytes
Sprague Dawley Rats
Flow Cytometry
Cell Death
Up-Regulation
Perfusion
Western Blotting
Cytokines
Inflammation

Keywords

  • Cell death
  • HMGB1
  • Heart
  • Interleukin
  • Ischemia-reperfusion
  • JNK
  • Pressure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

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title = "Pressure overload promotes HMGB1 signaling in the ischemic-reperfused heart",
abstract = "Damage-Associated Molecular Patterns (DAMPs) are released following tissue injury and can activate pro-inflammatory pathways. Prototypical DAMPs include the High-Mobility Group Box 1 (HMGB1) protein which is released from necrotic cells. In turn, HMGB1 promotes inflammation via mechanisms likely involving phosphorylation/ activation of c-Jun-NH2-Terminal Kinase (JNK) and production of the inflammasome-associated cytokine, interleukin-1β (IL-1β). We have shown that pressure overload increases infarct size in association with poorer functional recovery of the heart subjected to an ischemia-reperfusion insult. This study tested the hypothesis that pressure overload augments HMGB1 expression in association with increased IL-1β generation and JNK phosphorylation thereby contributing to increased tissue injury. Accordingly, hearts of male Sprague-Dawley rats were subjected to an ischemia (40 min) reperfusion (15 min) insult with perfusion pressure set at either 80 or 160 cm H 2 O. Thereafter, hearts were processed for flow cytometry and Western blot studies. The ischemic-reperfused hearts subjected to the high pressure displayed (a) greater expression of HMGB1 and IL-1β which were shown to also be generated by cardiomyocytes, (b) increased phosphoJNK levels and c) increased necrotic and apoptotic cell death. Collectively, the results suggest that pressure-related upregulation of HMGB1 signaling contributes to the pro-inflammatory response of the ischemic-reperfused heart involving augmented JNK activation and IL-1β generation.",
keywords = "Cell death, HMGB1, Heart, Interleukin, Ischemia-reperfusion, JNK, Pressure",
author = "Babak Baban and Liu, {Jun Yao} and Mozaffari, {Mahmood S}",
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AU - Liu, Jun Yao

AU - Mozaffari, Mahmood S

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N2 - Damage-Associated Molecular Patterns (DAMPs) are released following tissue injury and can activate pro-inflammatory pathways. Prototypical DAMPs include the High-Mobility Group Box 1 (HMGB1) protein which is released from necrotic cells. In turn, HMGB1 promotes inflammation via mechanisms likely involving phosphorylation/ activation of c-Jun-NH2-Terminal Kinase (JNK) and production of the inflammasome-associated cytokine, interleukin-1β (IL-1β). We have shown that pressure overload increases infarct size in association with poorer functional recovery of the heart subjected to an ischemia-reperfusion insult. This study tested the hypothesis that pressure overload augments HMGB1 expression in association with increased IL-1β generation and JNK phosphorylation thereby contributing to increased tissue injury. Accordingly, hearts of male Sprague-Dawley rats were subjected to an ischemia (40 min) reperfusion (15 min) insult with perfusion pressure set at either 80 or 160 cm H 2 O. Thereafter, hearts were processed for flow cytometry and Western blot studies. The ischemic-reperfused hearts subjected to the high pressure displayed (a) greater expression of HMGB1 and IL-1β which were shown to also be generated by cardiomyocytes, (b) increased phosphoJNK levels and c) increased necrotic and apoptotic cell death. Collectively, the results suggest that pressure-related upregulation of HMGB1 signaling contributes to the pro-inflammatory response of the ischemic-reperfused heart involving augmented JNK activation and IL-1β generation.

AB - Damage-Associated Molecular Patterns (DAMPs) are released following tissue injury and can activate pro-inflammatory pathways. Prototypical DAMPs include the High-Mobility Group Box 1 (HMGB1) protein which is released from necrotic cells. In turn, HMGB1 promotes inflammation via mechanisms likely involving phosphorylation/ activation of c-Jun-NH2-Terminal Kinase (JNK) and production of the inflammasome-associated cytokine, interleukin-1β (IL-1β). We have shown that pressure overload increases infarct size in association with poorer functional recovery of the heart subjected to an ischemia-reperfusion insult. This study tested the hypothesis that pressure overload augments HMGB1 expression in association with increased IL-1β generation and JNK phosphorylation thereby contributing to increased tissue injury. Accordingly, hearts of male Sprague-Dawley rats were subjected to an ischemia (40 min) reperfusion (15 min) insult with perfusion pressure set at either 80 or 160 cm H 2 O. Thereafter, hearts were processed for flow cytometry and Western blot studies. The ischemic-reperfused hearts subjected to the high pressure displayed (a) greater expression of HMGB1 and IL-1β which were shown to also be generated by cardiomyocytes, (b) increased phosphoJNK levels and c) increased necrotic and apoptotic cell death. Collectively, the results suggest that pressure-related upregulation of HMGB1 signaling contributes to the pro-inflammatory response of the ischemic-reperfused heart involving augmented JNK activation and IL-1β generation.

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