Atrial AMP-activated protein kinase is critical for prevention of dysregulation of electrical excitability and atrial fibrillation.
Arrhythmias
Cardiology
Protein kinases
Journal
JCI insight
ISSN: 2379-3708
Titre abrégé: JCI Insight
Pays: United States
ID NLM: 101676073
Informations de publication
Date de publication:
22 04 2022
22 04 2022
Historique:
received:
11
06
2020
accepted:
23
02
2022
entrez:
22
4
2022
pubmed:
23
4
2022
medline:
26
4
2022
Statut:
epublish
Résumé
Metabolic stress is an important cause of pathological atrial remodeling and atrial fibrillation. AMPK is a ubiquitous master metabolic regulator, yet its biological function in the atria is poorly understood in both health and disease. We investigated the impact of atrium-selective cardiac AMPK deletion on electrophysiological and structural remodeling in mice. Loss of atrial AMPK expression caused atrial changes in electrophysiological properties and atrial ectopic activity prior to the onset of spontaneous atrial fibrillation. Concomitant transcriptional downregulation of connexins and atrial ion channel subunits manifested with delayed left atrial activation and repolarization. The early molecular and electrophysiological abnormalities preceded left atrial structural remodeling and interstitial fibrosis. AMPK inactivation induced downregulation of transcription factors (Mef2c and Pitx2c) linked to connexin and ion channel transcriptional reprogramming. Thus, AMPK plays an essential homeostatic role in atria, protecting against adverse remodeling potentially by regulating key transcription factors that control the expression of atrial ion channels and gap junction proteins.
Identifiants
pubmed: 35451373
pii: 141213
doi: 10.1172/jci.insight.141213
pmc: PMC9089788
doi:
pii:
Substances chimiques
Connexins
0
Ion Channels
0
Transcription Factors
0
AMP-Activated Protein Kinases
EC 2.7.11.31
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL149344
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL148008
Pays : United States
Organisme : NIH HHS
ID : S10 OD021845
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL128069
Pays : United States
Organisme : NHLBI NIH HHS
ID : R21 HL165147
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137259
Pays : United States
Références
Cardiovasc Diabetol. 2017 Sep 29;16(1):120
pubmed: 28962617
Circulation. 2003 May 13;107(18):2355-60
pubmed: 12695296
Development. 2001 Jun;128(11):2039-48
pubmed: 11493526
J Vis Exp. 2013 Sep 06;(79):
pubmed: 24056408
Circ Res. 2000 Mar 17;86(5):571-9
pubmed: 10720419
Development. 1999 Dec;126(24):5749-58
pubmed: 10572050
Circulation. 2003 Sep 23;108(12):1461-8
pubmed: 12952837
Card Electrophysiol Clin. 2021 Mar;13(1):25-35
pubmed: 33516403
Circulation. 2015 Aug 18;132(7):567-77
pubmed: 26187182
Circulation. 2011 Nov 15;124(20):2264-74
pubmed: 22083148
Circulation. 1999 Jul 6;100(1):87-95
pubmed: 10393686
Am J Physiol Endocrinol Metab. 2006 May;290(5):E780-8
pubmed: 16332922
Proc Natl Acad Sci U S A. 2010 May 25;107(21):9753-8
pubmed: 20457925
Biochem Biophys Res Commun. 2005 Jul 15;332(4):1012-9
pubmed: 15922306
J Am Coll Cardiol. 2010 May 25;55(21):2330-42
pubmed: 20488304
J Cardiovasc Pharmacol. 2015 Dec;66(6):523-9
pubmed: 26335221
Circulation. 2000 Jun 6;101(22):2631-8
pubmed: 10840016
Circulation. 2008 Apr 15;117(15):1927-35
pubmed: 18378609
Circulation. 2012 May 1;125(17):2059-70
pubmed: 22456474
JAMA. 1994 Mar 16;271(11):840-4
pubmed: 8114238
Circ Res. 2009 Feb 13;104(3):403-11
pubmed: 19096023
J Mol Cell Cardiol. 2011 Feb;50(2):337-45
pubmed: 20974149
Nature. 2007 Jul 19;448(7151):353-7
pubmed: 17603472
N Engl J Med. 2006 Jun 22;354(25):2677-88
pubmed: 16790700
Circulation. 2010 Jul 20;122(3):282-92
pubmed: 20606117
Circulation. 2009 May 19;119(19):2568-77
pubmed: 19414638
Science. 1997 May 30;276(5317):1404-7
pubmed: 9162005
Nat Rev Cardiol. 2019 Sep;16(9):519-537
pubmed: 31028357
Cell. 2010 Aug 6;142(3):375-86
pubmed: 20691899
Circulation. 2001 Oct 2;104(14):1664-9
pubmed: 11581146
J Am Coll Cardiol. 2015 Jul 7;66(1):47-58
pubmed: 26139058
Am J Physiol. 1999 Aug;277(2):H643-9
pubmed: 10444490
Methods Mol Biol. 2018;1816:133-143
pubmed: 29987816
Hypertension. 2008 Nov;52(5):918-24
pubmed: 18838626
Curr Biol. 2000 Oct 19;10(20):1247-55
pubmed: 11069105
Circ Res. 2012 Aug 31;111(6):800-14
pubmed: 22935535
Development. 1999 Oct;126(20):4643-51
pubmed: 10498698
Circulation. 1997 Feb 4;95(3):572-6
pubmed: 9024141
Am J Cardiol. 2009 Dec 1;104(11):1534-9
pubmed: 19932788
Proc Natl Acad Sci U S A. 2014 Jun 24;111(25):9181-6
pubmed: 24927531
J Clin Invest. 2003 May;111(10):1529-36
pubmed: 12750402
Cardiovasc Res. 2002 May;54(2):361-79
pubmed: 12062341
JCI Insight. 2019 Sep 5;4(17):
pubmed: 31484822
J Clin Invest. 2004 Aug;114(4):495-503
pubmed: 15314686
Circ Cardiovasc Genet. 2011 Jun;4(3):269-79
pubmed: 21511879
Neuroimage. 2006 Jul 1;31(3):1116-28
pubmed: 16545965
Front Physiol. 2020 Feb 19;11:108
pubmed: 32140110
J Am Coll Cardiol. 2008 Feb 26;51(8):802-9
pubmed: 18294563
Diabetes. 2007 Mar;56(3):836-48
pubmed: 17327455
J Mol Cell Cardiol. 2014 Nov;76:159-68
pubmed: 25200600
Biochim Biophys Acta. 1996 May 31;1301(1-2):67-75
pubmed: 8652652
EBioMedicine. 2018 Feb;28:194-209
pubmed: 29343420
Cardiovasc Res. 2015 Oct 1;108(1):197-208
pubmed: 26378152