Differential regulation of TNF receptors by vagal nerve stimulation protects heart against acute ischemic injury

Rajesh G. Katare, Motonori Ando, Yoshihiko Kakinuma, Mikihiko Arikawa, Fumiyasu Yamasaki, Takayuki Sato

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Vagal nerve stimulation (VS) has been reported to improve the survival after both acute and chronic myocardial infarction through the release of neurotransmitter ACh. However, the precise mechanism behind its beneficial effect is still unknown. In this study, we demonstrate the upregulation of tumor necrosis factor-alpha (TNF-α) and its cell survival TNF receptor-2 (TNFR2) as the mechanism behind VS induced myocardial protection.We investigated the effects of efferent VS on myocardial ischemic injury with in vivo and in vitro mouse models. In in vivo hearts VS significantly increased the expression of TNF-α both at the messenger and protein level after 3-hours of myocardial ischemia. In the in vitro studies ACh treatment before hypoxia, induced a significant upregulation of TNF-α compared to the untreated cardiomyocytes. Immunofluorescence analysis confirmed the synthesis of TNF-α by cardiomyocytes both in vivo and in vitro. VS also significantly reduced the myocardial infarct size (23.9±5.7% vs. 56±1.9%) and activated the cell survival Akt cascade system. Further, ACh upregulated the cell survival TNFR2 expression, while downregulating the cell destructive TNF receptor 1 (TNFR1) expression. These results were confirmed using the TNF receptors deficient mice, where the VS mediated protection was lost both in vivo and in vitro in TNFR2 (TNFR2-/-) and TNF receptors double knock out (TNFR1-/-2-/-) mice.VS and ACh protects the heart against acute ischemia or hypoxic injury by differentially regulating the TNF receptor subtypes.

Original languageEnglish
Pages (from-to)234-244
Number of pages11
JournalJournal of Molecular and Cellular Cardiology
Volume49
Issue number2
DOIs
Publication statusPublished - Aug 2010

Fingerprint

Vagus Nerve Stimulation
Tumor Necrosis Factor Receptors
Wounds and Injuries
Tumor Necrosis Factor-alpha
Cell Survival
Cardiac Myocytes
Up-Regulation
Myocardial Infarction
Myocardial Ischemia
Fluorescent Antibody Technique
Neurotransmitter Agents
Down-Regulation
Ischemia
In Vitro Techniques

Keywords

  • Apoptosis
  • Myocardial Ischemia
  • TNF receptors
  • Tumor necrosis factor-α
  • Vagus Nerve

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Differential regulation of TNF receptors by vagal nerve stimulation protects heart against acute ischemic injury. / Katare, Rajesh G.; Ando, Motonori; Kakinuma, Yoshihiko; Arikawa, Mikihiko; Yamasaki, Fumiyasu; Sato, Takayuki.

In: Journal of Molecular and Cellular Cardiology, Vol. 49, No. 2, 08.2010, p. 234-244.

Research output: Contribution to journalArticle

Katare, Rajesh G. ; Ando, Motonori ; Kakinuma, Yoshihiko ; Arikawa, Mikihiko ; Yamasaki, Fumiyasu ; Sato, Takayuki. / Differential regulation of TNF receptors by vagal nerve stimulation protects heart against acute ischemic injury. In: Journal of Molecular and Cellular Cardiology. 2010 ; Vol. 49, No. 2. pp. 234-244.
@article{c35b7c9aba2841e5b1f844a11ea732ee,
title = "Differential regulation of TNF receptors by vagal nerve stimulation protects heart against acute ischemic injury",
abstract = "Vagal nerve stimulation (VS) has been reported to improve the survival after both acute and chronic myocardial infarction through the release of neurotransmitter ACh. However, the precise mechanism behind its beneficial effect is still unknown. In this study, we demonstrate the upregulation of tumor necrosis factor-alpha (TNF-α) and its cell survival TNF receptor-2 (TNFR2) as the mechanism behind VS induced myocardial protection.We investigated the effects of efferent VS on myocardial ischemic injury with in vivo and in vitro mouse models. In in vivo hearts VS significantly increased the expression of TNF-α both at the messenger and protein level after 3-hours of myocardial ischemia. In the in vitro studies ACh treatment before hypoxia, induced a significant upregulation of TNF-α compared to the untreated cardiomyocytes. Immunofluorescence analysis confirmed the synthesis of TNF-α by cardiomyocytes both in vivo and in vitro. VS also significantly reduced the myocardial infarct size (23.9±5.7{\%} vs. 56±1.9{\%}) and activated the cell survival Akt cascade system. Further, ACh upregulated the cell survival TNFR2 expression, while downregulating the cell destructive TNF receptor 1 (TNFR1) expression. These results were confirmed using the TNF receptors deficient mice, where the VS mediated protection was lost both in vivo and in vitro in TNFR2 (TNFR2-/-) and TNF receptors double knock out (TNFR1-/-2-/-) mice.VS and ACh protects the heart against acute ischemia or hypoxic injury by differentially regulating the TNF receptor subtypes.",
keywords = "Apoptosis, Myocardial Ischemia, TNF receptors, Tumor necrosis factor-α, Vagus Nerve",
author = "Katare, {Rajesh G.} and Motonori Ando and Yoshihiko Kakinuma and Mikihiko Arikawa and Fumiyasu Yamasaki and Takayuki Sato",
year = "2010",
month = "8",
doi = "10.1016/j.yjmcc.2010.03.007",
language = "English",
volume = "49",
pages = "234--244",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Differential regulation of TNF receptors by vagal nerve stimulation protects heart against acute ischemic injury

AU - Katare, Rajesh G.

AU - Ando, Motonori

AU - Kakinuma, Yoshihiko

AU - Arikawa, Mikihiko

AU - Yamasaki, Fumiyasu

AU - Sato, Takayuki

PY - 2010/8

Y1 - 2010/8

N2 - Vagal nerve stimulation (VS) has been reported to improve the survival after both acute and chronic myocardial infarction through the release of neurotransmitter ACh. However, the precise mechanism behind its beneficial effect is still unknown. In this study, we demonstrate the upregulation of tumor necrosis factor-alpha (TNF-α) and its cell survival TNF receptor-2 (TNFR2) as the mechanism behind VS induced myocardial protection.We investigated the effects of efferent VS on myocardial ischemic injury with in vivo and in vitro mouse models. In in vivo hearts VS significantly increased the expression of TNF-α both at the messenger and protein level after 3-hours of myocardial ischemia. In the in vitro studies ACh treatment before hypoxia, induced a significant upregulation of TNF-α compared to the untreated cardiomyocytes. Immunofluorescence analysis confirmed the synthesis of TNF-α by cardiomyocytes both in vivo and in vitro. VS also significantly reduced the myocardial infarct size (23.9±5.7% vs. 56±1.9%) and activated the cell survival Akt cascade system. Further, ACh upregulated the cell survival TNFR2 expression, while downregulating the cell destructive TNF receptor 1 (TNFR1) expression. These results were confirmed using the TNF receptors deficient mice, where the VS mediated protection was lost both in vivo and in vitro in TNFR2 (TNFR2-/-) and TNF receptors double knock out (TNFR1-/-2-/-) mice.VS and ACh protects the heart against acute ischemia or hypoxic injury by differentially regulating the TNF receptor subtypes.

AB - Vagal nerve stimulation (VS) has been reported to improve the survival after both acute and chronic myocardial infarction through the release of neurotransmitter ACh. However, the precise mechanism behind its beneficial effect is still unknown. In this study, we demonstrate the upregulation of tumor necrosis factor-alpha (TNF-α) and its cell survival TNF receptor-2 (TNFR2) as the mechanism behind VS induced myocardial protection.We investigated the effects of efferent VS on myocardial ischemic injury with in vivo and in vitro mouse models. In in vivo hearts VS significantly increased the expression of TNF-α both at the messenger and protein level after 3-hours of myocardial ischemia. In the in vitro studies ACh treatment before hypoxia, induced a significant upregulation of TNF-α compared to the untreated cardiomyocytes. Immunofluorescence analysis confirmed the synthesis of TNF-α by cardiomyocytes both in vivo and in vitro. VS also significantly reduced the myocardial infarct size (23.9±5.7% vs. 56±1.9%) and activated the cell survival Akt cascade system. Further, ACh upregulated the cell survival TNFR2 expression, while downregulating the cell destructive TNF receptor 1 (TNFR1) expression. These results were confirmed using the TNF receptors deficient mice, where the VS mediated protection was lost both in vivo and in vitro in TNFR2 (TNFR2-/-) and TNF receptors double knock out (TNFR1-/-2-/-) mice.VS and ACh protects the heart against acute ischemia or hypoxic injury by differentially regulating the TNF receptor subtypes.

KW - Apoptosis

KW - Myocardial Ischemia

KW - TNF receptors

KW - Tumor necrosis factor-α

KW - Vagus Nerve

UR - http://www.scopus.com/inward/record.url?scp=77953694186&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953694186&partnerID=8YFLogxK

U2 - 10.1016/j.yjmcc.2010.03.007

DO - 10.1016/j.yjmcc.2010.03.007

M3 - Article

VL - 49

SP - 234

EP - 244

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 2

ER -