In vivo transfection of manganese superoxide dismutase gene or nuclear factor κB shRNA in nodose ganglia improves aortic baroreceptor function in heart failure rats

Dongze Zhang, Jinxu Liu, Huiyin Tu, Robert Leo Muelleman, Kurtis G. Cornish, Yulong Li

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Arterial baroreflex sensitivity is attenuated in chronic heart failure (CHF) state, which is associated with cardiac arrhythmias and sudden cardiac death in patients with CHF. Our previous study showed that CHF-induced sodium channel dysfunction in the baroreceptor neurons was involved in the blunted baroreflex sensitivity in CHF rats. Mitochondria-derived superoxide overproduction decreased expression and activation of the sodium channels in the baroreceptor neurons from CHF rats. However, the molecular mechanisms responsible for the sodium channel dysfunction in the baroreceptor neurons from CHF rats remain unknown. We tested the involvement of nuclear factor κB (NFκB) in the sodium channel dysfunction and evaluated the effects of in vivo transfection of manganese superoxide dismutase gene and NFκB shRNA on the baroreflex function in CHF rats. CHF was developed at 6 to 8 weeks after left coronary artery ligation in adult rats. Western blot and chromatin immunoprecipitation data showed that phosphorylated NFκB p65 and ability of NFκB p65 binding to the sodium channel promoter were increased in the nodose ganglia from CHF rats. In vivo transfection of adenoviral manganese superoxide dismutase gene or lentiviral NFκB p65 shRNA into the nodose ganglia partially reversed CHF-reduced sodium channel expression and cell excitability in the baroreceptor neurons and improved CHF-blunted arterial baroreflex sensitivity. Additionally, transfection of adenoviral manganese superoxide dismutase also inhibited the augmentation of phosphorylated NFκB p65 in the nodose neurons from CHF rats. The present study suggests that superoxide-NFκB signaling contributes to CHF-induced baroreceptor dysfunction and resultant impairment of baroreflex function.

Original languageEnglish (US)
Pages (from-to)88-95
Number of pages8
JournalHypertension
Volume63
Issue number1
DOIs
StatePublished - Jan 1 2014

Fingerprint

Nodose Ganglion
Pressoreceptors
Small Interfering RNA
Superoxide Dismutase
Transfection
Heart Failure
Sodium Channels
Genes
Baroreflex
Neurons
Superoxides
Chromatin Immunoprecipitation
Sudden Cardiac Death

Keywords

  • Baroreflex
  • Heart failure
  • Pressoreceptors
  • Sodium channels
  • Superoxides

ASJC Scopus subject areas

  • Internal Medicine

Cite this

In vivo transfection of manganese superoxide dismutase gene or nuclear factor κB shRNA in nodose ganglia improves aortic baroreceptor function in heart failure rats. / Zhang, Dongze; Liu, Jinxu; Tu, Huiyin; Muelleman, Robert Leo; Cornish, Kurtis G.; Li, Yulong.

In: Hypertension, Vol. 63, No. 1, 01.01.2014, p. 88-95.

Research output: Contribution to journalArticle

@article{2e96c6a5d4dd485baf152f58ae09bece,
title = "In vivo transfection of manganese superoxide dismutase gene or nuclear factor κB shRNA in nodose ganglia improves aortic baroreceptor function in heart failure rats",
abstract = "Arterial baroreflex sensitivity is attenuated in chronic heart failure (CHF) state, which is associated with cardiac arrhythmias and sudden cardiac death in patients with CHF. Our previous study showed that CHF-induced sodium channel dysfunction in the baroreceptor neurons was involved in the blunted baroreflex sensitivity in CHF rats. Mitochondria-derived superoxide overproduction decreased expression and activation of the sodium channels in the baroreceptor neurons from CHF rats. However, the molecular mechanisms responsible for the sodium channel dysfunction in the baroreceptor neurons from CHF rats remain unknown. We tested the involvement of nuclear factor κB (NFκB) in the sodium channel dysfunction and evaluated the effects of in vivo transfection of manganese superoxide dismutase gene and NFκB shRNA on the baroreflex function in CHF rats. CHF was developed at 6 to 8 weeks after left coronary artery ligation in adult rats. Western blot and chromatin immunoprecipitation data showed that phosphorylated NFκB p65 and ability of NFκB p65 binding to the sodium channel promoter were increased in the nodose ganglia from CHF rats. In vivo transfection of adenoviral manganese superoxide dismutase gene or lentiviral NFκB p65 shRNA into the nodose ganglia partially reversed CHF-reduced sodium channel expression and cell excitability in the baroreceptor neurons and improved CHF-blunted arterial baroreflex sensitivity. Additionally, transfection of adenoviral manganese superoxide dismutase also inhibited the augmentation of phosphorylated NFκB p65 in the nodose neurons from CHF rats. The present study suggests that superoxide-NFκB signaling contributes to CHF-induced baroreceptor dysfunction and resultant impairment of baroreflex function.",
keywords = "Baroreflex, Heart failure, Pressoreceptors, Sodium channels, Superoxides",
author = "Dongze Zhang and Jinxu Liu and Huiyin Tu and Muelleman, {Robert Leo} and Cornish, {Kurtis G.} and Yulong Li",
year = "2014",
month = "1",
day = "1",
doi = "10.1161/HYPERTENSIONAHA.113.02057",
language = "English (US)",
volume = "63",
pages = "88--95",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - In vivo transfection of manganese superoxide dismutase gene or nuclear factor κB shRNA in nodose ganglia improves aortic baroreceptor function in heart failure rats

AU - Zhang, Dongze

AU - Liu, Jinxu

AU - Tu, Huiyin

AU - Muelleman, Robert Leo

AU - Cornish, Kurtis G.

AU - Li, Yulong

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Arterial baroreflex sensitivity is attenuated in chronic heart failure (CHF) state, which is associated with cardiac arrhythmias and sudden cardiac death in patients with CHF. Our previous study showed that CHF-induced sodium channel dysfunction in the baroreceptor neurons was involved in the blunted baroreflex sensitivity in CHF rats. Mitochondria-derived superoxide overproduction decreased expression and activation of the sodium channels in the baroreceptor neurons from CHF rats. However, the molecular mechanisms responsible for the sodium channel dysfunction in the baroreceptor neurons from CHF rats remain unknown. We tested the involvement of nuclear factor κB (NFκB) in the sodium channel dysfunction and evaluated the effects of in vivo transfection of manganese superoxide dismutase gene and NFκB shRNA on the baroreflex function in CHF rats. CHF was developed at 6 to 8 weeks after left coronary artery ligation in adult rats. Western blot and chromatin immunoprecipitation data showed that phosphorylated NFκB p65 and ability of NFκB p65 binding to the sodium channel promoter were increased in the nodose ganglia from CHF rats. In vivo transfection of adenoviral manganese superoxide dismutase gene or lentiviral NFκB p65 shRNA into the nodose ganglia partially reversed CHF-reduced sodium channel expression and cell excitability in the baroreceptor neurons and improved CHF-blunted arterial baroreflex sensitivity. Additionally, transfection of adenoviral manganese superoxide dismutase also inhibited the augmentation of phosphorylated NFκB p65 in the nodose neurons from CHF rats. The present study suggests that superoxide-NFκB signaling contributes to CHF-induced baroreceptor dysfunction and resultant impairment of baroreflex function.

AB - Arterial baroreflex sensitivity is attenuated in chronic heart failure (CHF) state, which is associated with cardiac arrhythmias and sudden cardiac death in patients with CHF. Our previous study showed that CHF-induced sodium channel dysfunction in the baroreceptor neurons was involved in the blunted baroreflex sensitivity in CHF rats. Mitochondria-derived superoxide overproduction decreased expression and activation of the sodium channels in the baroreceptor neurons from CHF rats. However, the molecular mechanisms responsible for the sodium channel dysfunction in the baroreceptor neurons from CHF rats remain unknown. We tested the involvement of nuclear factor κB (NFκB) in the sodium channel dysfunction and evaluated the effects of in vivo transfection of manganese superoxide dismutase gene and NFκB shRNA on the baroreflex function in CHF rats. CHF was developed at 6 to 8 weeks after left coronary artery ligation in adult rats. Western blot and chromatin immunoprecipitation data showed that phosphorylated NFκB p65 and ability of NFκB p65 binding to the sodium channel promoter were increased in the nodose ganglia from CHF rats. In vivo transfection of adenoviral manganese superoxide dismutase gene or lentiviral NFκB p65 shRNA into the nodose ganglia partially reversed CHF-reduced sodium channel expression and cell excitability in the baroreceptor neurons and improved CHF-blunted arterial baroreflex sensitivity. Additionally, transfection of adenoviral manganese superoxide dismutase also inhibited the augmentation of phosphorylated NFκB p65 in the nodose neurons from CHF rats. The present study suggests that superoxide-NFκB signaling contributes to CHF-induced baroreceptor dysfunction and resultant impairment of baroreflex function.

KW - Baroreflex

KW - Heart failure

KW - Pressoreceptors

KW - Sodium channels

KW - Superoxides

UR - http://www.scopus.com/inward/record.url?scp=84891626440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84891626440&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.113.02057

DO - 10.1161/HYPERTENSIONAHA.113.02057

M3 - Article

VL - 63

SP - 88

EP - 95

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 1

ER -