Abstract:
:Oxidative stress plays a crucial role in disruption of neovascularization by alterations in thioredoxin 1 (Trx1) expression and its interaction with other proteins after myocardial infarction (MI). We previously showed that Trx1 has angiogenic properties, but the possible therapeutic significance of overexpressing Trx1 in chronic MI has not been elucidated. Therefore, we explored the angiogenic and cardioprotective potential of Trx1 in an in vivo MI model using transgenic mice overexpressing Trx1. Wild-type (W) and Trx1 transgenic (Trx1(Tg/+)) mice were randomized into W sham (WS), Trx1(Tg/+) sham (TS), WMI, and TMI. MI was induced by permanent occlusion of LAD coronary artery. Hearts from mice overexpressing Trx1 exhibited reduced fibrosis and oxidative stress and attenuated cardiomyocyte apoptosis along with increased vessel formation compared to WMI. We found significant inhibition of Trx1 regulating proteins, TXNIP and AKAP 12, and increased p-Akt, p-eNOS, p-GSK-3β, HIF-1α, β-catenin, VEGF, Bcl-2, and survivin expression in TMI compared to WMI. Echocardiography performed 30days after MI revealed significant improvement in myocardial functions in TMI compared to WMI. Our study identifies a potential role for Trx1 overexpression and its association with its regulatory proteins TXNIP, AKAP12, and subsequent activation of Akt/GSK-3β/β-catenin/HIF-1α-mediated VEGF and eNOS expression in inducing angiogenesis and reduced ventricular remodeling. Hence, Trx1 and other proteins identified in our study may prove to be potential therapeutic targets in the treatment of ischemic heart disease.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Adluri RS,Thirunavukkarasu M,Zhan L,Akita Y,Samuel SM,Otani H,Ho YS,Maulik G,Maulik Ndoi
10.1016/j.yjmcc.2010.11.002subject
Has Abstractpub_date
2011-01-01 00:00:00pages
239-47issue
1eissn
0022-2828issn
1095-8584pii
S0022-2828(10)00434-7journal_volume
50pub_type
杂志文章abstract::Hypothermic cardioplegic solutions are currently used to preserve cardiac function during transportation. However, it has been shown that end-diastolic compliance decreases in donor hearts during reperfusion. Excessively cold temperatures may affect membrane-bound enzymes (Ca2+ ATPase and Ca2+ uptake) which are necess...
journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0207
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1119
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.08.011
更新日期:2010-12-01 00:00:00
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2007.09.008
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.07.014
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.01.006
更新日期:2017-02-01 00:00:00
abstract::Atrial fibrosis has been strongly associated with the presence of heart diseases/arrhythmias, including congestive heart failure (CHF) and atrial fibrillation (AF). Inducibility of AF as a result of atrial fibrosis has been the subject of intense recent investigation since it is the most commonly encountered arrhythmi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
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abstract::Aftercontractions induced by beta-adrenoceptor stimulation in human and guinea-pig cardiomyocytes may be related to changes in action potential duration (APD). We investigated the effects of altering APD during the occurrence of isoproterenol-induced aftercontractions, using the KATP channel openers cromakalim and lem...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0385
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.013
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0871
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90805-5
更新日期:1989-10-01 00:00:00
abstract::Numerous studies suggest that in adult hearts myocardial ischemic injury is in part the result of proton stimulation of Na/H exchange which increases intracellular Na (Nai) and thus leads to increases in intracellular Ca concentration ( [Ca]i) due to changes in Na/Ca exchange flux. Corollary to the hypothesis, inhibit...
journal_title:Journal of molecular and cellular cardiology
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doi:10.1006/jmcc.1997.0442
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93384-v
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journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90673-1
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abstract::The sympathetic nervous system is the main stimulator of cardiac function. While acute activation of the β-adrenoceptors exerts positive inotropic and lusitropic effects by increasing cAMP and Ca2+, chronically enhanced sympathetic tone with changed β-adrenergic signaling leads to alterations of gene expression and re...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.12.001
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abstract::Catecholaminergic polymorphic ventricular tachycardia (CPVT) is linked to mutations in the cardiac ryanodine receptor (RyR2) or calsequestrin. We recently found that the drug flecainide inhibits RyR2 channels and prevents CPVT in mice and humans. Here we compared the effects of flecainide and tetracaine, a known RyR2 ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.005
更新日期:2010-02-01 00:00:00