当前位置： SCI文献检索 > HEART RHYTHM期刊下所有文献 > Targeted nonviral gene-based inhibition of Gα(i/o)-mediated vagal signaling in the posterior left atrium decreases vagal-induced atrial fibrillation.

Targeted nonviral gene-based inhibition of Gα(i/o)-mediated vagal signaling in the posterior left atrium decreases vagal-induced atrial fibrillation.

Abstract：

BACKGROUND:Pharmacologic and ablative therapies for atrial fibrillation (AF) have suboptimal efficacy. Newer gene-based approaches that target specific mechanisms underlying AF are likely to be more efficacious in treating AF. Parasympathetic signaling appears to be an important contributor to AF substrate. OBJECTIVE:The purpose of this study was to develop a nonviral gene-based strategy to selectively inhibit vagal signaling in the left atrium and thereby suppress vagal-induced AF. METHODS:In eight dogs, plasmid DNA vectors (minigenes) expressing Gα(i) C-terminal peptide (Gα(i)ctp) was injected in the posterior left atrium either alone or in combination with minigene expressing Gα(o)ctp, followed by electroporation. In five control dogs, minigene expressing scrambled peptide (Gα(R)ctp) was injected. Vagal- and carbachol-induced left atrial effective refractory periods (ERPs), AF inducibility, and Gα(i/o)ctp expression were assessed 3 days following minigene delivery. RESULTS:Vagal stimulation- and carbachol-induced effective refractory period shortening and AF inducibility were significantly attenuated in atria receiving a Gα(i2)ctp-expressing minigene and were nearly eliminated in atria receiving both Gα(i2)ctp- and Gα(o1)ctp-expressing minigenes. CONCLUSION:Inhibition of both G(i) and G(o) proteins is necessary to abrogate vagal-induced AF in the left atrium and can be achieved via constitutive expression of Gα(i/o)ctps expressed by nonviral plasmid vectors delivered to the posterior left atrium.

journal_name

Heart Rhythm

journal_title

Heart rhythm

authors

Aistrup GL,Cokic I,Ng J,Gordon D,Koduri H,Browne S,Arapi D,Segon Y,Goldstein J,Angulo A,Wasserstrom JA,Goldberger JJ,Kadish AH,Arora R

doi

10.1016/j.hrthm.2011.06.018

subject

Has Abstract

pub_date

2011-11-01 00:00:00

pages

1722-9

issue

11

eissn

1547-5271

issn

1556-3871

pii

S1547-5271(11)00706-5

journal_volume

8

pub_type

杂志文章

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