Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.
Journal
The Journal of general physiology
ISSN: 1540-7748
Titre abrégé: J Gen Physiol
Pays: United States
ID NLM: 2985110R
Informations de publication
Date de publication:
06 Nov 2023
06 Nov 2023
Historique:
received:
16
11
2022
revised:
20
05
2023
accepted:
29
08
2023
pmc-release:
03
04
2024
medline:
1
11
2023
pubmed:
3
10
2023
entrez:
3
10
2023
Statut:
ppublish
Résumé
Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients. The aim of this investigation was to determine whether transmural conduction gradients are modified in a rat model of pericardial adiposity. Adult Sprague-Dawley rats were fed control/high-fat diets for 15 wk. Left ventricular 300 µm tangential slices were generated from the endocardium to the epicardium, and conduction was mapped using microelectrode arrays. Slices were then histologically processed to assess fibrosis and cardiomyocyte lipid status. Conduction velocity was significantly greater in epicardial versus endocardial slices in control rats, supporting the concept of a transmural conduction gradient. High-fat diet feeding increased pericardial adiposity and abolished the transmural conduction gradient. Slowed epicardial conduction in epicardial slices strongly correlated with an increase in cardiomyocyte lipid content, but not fibrosis. The positive transmural conduction gradient reported here represents a physiological property of the ventricular activation sequence that likely protects against reentry. The absence of this gradient, secondary to conduction slowing and cardiomyocyte lipid accumulation, specifically in the epicardium, indicates a novel mechanism by which pericardial adiposity may exacerbate ventricular arrhythmias.
Identifiants
pubmed: 37787979
pii: 276312
doi: 10.1085/jgp.202213296
pmc: PMC10547601
pii:
doi:
Substances chimiques
Lipids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
ID : 221650/Z/20/Z
Pays : United Kingdom
Organisme : British Heart Foundation
ID : RG/17/15/33106
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/12/34204
Pays : United Kingdom
Organisme : British Heart Foundation
ID : PG/17/55/33087
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : British Heart Foundation
ID : FS/19/16/34169
Pays : United Kingdom
Informations de copyright
© 2023 Wells et al.
Références
Nat Protoc. 2017 Dec;12(12):2623-2639
pubmed: 29189769
J Am Coll Cardiol. 2020 Sep 8;76(10):1197-1211
pubmed: 32883413
J Mol Cell Cardiol. 2016 Jan;90:38-46
pubmed: 26654778
Cardiovasc Res. 2003 Apr 1;58(1):66-75
pubmed: 12667947
Endocrinology. 2003 Aug;144(8):3483-90
pubmed: 12865329
Cells. 2021 Oct 28;10(11):
pubmed: 34831145
Prog Biophys Mol Biol. 2016 Jan;120(1-3):222-35
pubmed: 26790342
Growth Horm IGF Res. 2018 Oct - Dec;42-43:1-7
pubmed: 30025286
Circ Heart Fail. 2011 Jan;4(1):36-43
pubmed: 21071547
Adipocyte. 2015 Jul 15;5(1):11-21
pubmed: 27144092
J Am Coll Cardiol. 2015 Jul 7;66(1):1-11
pubmed: 26139051
Atherosclerosis. 2015 Aug;241(2):607-14
pubmed: 26116961
Anat Rec. 1988 Feb;220(2):132-7
pubmed: 3354856
Eur Heart J. 2015 Apr 1;36(13):795-805a
pubmed: 23525094
Cardiovasc Diabetol. 2015 Jul 14;14:87
pubmed: 26169175
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):E771-E780
pubmed: 28096344
Heart Rhythm. 2019 Oct;16(10):1492-1498
pubmed: 31202898
Circ J. 2016 Jul 25;80(8):1726-33
pubmed: 27301329
Circulation. 1970 Jun;41(6):899-912
pubmed: 5482907
Circ Res. 2007 Oct 12;101(8):759-67
pubmed: 17932333
Circulation. 2021 May 25;143(21):e984-e1010
pubmed: 33882682
Cell Physiol Biochem. 2009;24(5-6):527-36
pubmed: 19910693
J Am Heart Assoc. 2018 Jun 1;7(11):
pubmed: 29858360
Biophys J. 1996 Mar;70(3):1494-504
pubmed: 8785306
Lab Invest. 2005 Oct;85(10):1224-37
pubmed: 16127430
J Am Heart Assoc. 2018 Dec 4;7(23):e009975
pubmed: 30571602
Sci Rep. 2018 May 2;8(1):6947
pubmed: 29720607
Circ Res. 2001 Apr 27;88(8):839-48
pubmed: 11325877
FASEB J. 2004 Nov;18(14):1692-700
pubmed: 15522914
Circulation. 2011 Dec 20;124(25):2812-21
pubmed: 22124376
Prog Cardiovasc Dis. 2018 Jul - Aug;61(2):124-135
pubmed: 29698642
Circ Arrhythm Electrophysiol. 2011 Oct;4(5):692-703
pubmed: 21750274
Circ Arrhythm Electrophysiol. 2019 Nov;12(11):e007573
pubmed: 31665913
Int J Obes (Lond). 2019 Aug;43(8):1491-1492
pubmed: 30967607
J Am Coll Cardiol. 2021 Oct 26;78(17):1730-1745
pubmed: 34674819
J Physiol. 1999 Sep 15;519 Pt 3:841-50
pubmed: 10457095
Compr Physiol. 2012 Jan;2(1):31-68
pubmed: 23728970
J Physiol. 2018 Sep;596(17):3951-3965
pubmed: 29928770
Cardiovasc Res. 2015 Oct 1;108(1):188-96
pubmed: 26209251