Abstract:
:We compared the effects of linagliptin (Lina, a DPP4 inhibitor) and GLP-1 receptor activation by exenatide followed by exendin-4 in an infusion pump (EX) on infarct size (IS), post-infarction activation of the inflammasome and remodeling in wild-type (WT) and db/db diabetic mice. Mice underwent 30 min ischemia followed by 24 h reperfusion. IS was assessed by TTC. Additional mice underwent permanent coronary artery occlusion. Echocardiography was performed 2w after infarction. Activation of the inflammasome in the border zone of the infarction was assessed by rt-PCR and ELISA 2w after reperfusion. Further in vitro experiments were done using primary human cardiofibroblasts and cardiomyocytes exposed to simulated ischemia-reoxygenation. Lina and EX limited IS in both the WT and the db/db mice. Lina and EX equally improved ejection fraction in both the WT and the db/db mice. mRNA levels of ASC, NALP3, IL-1β, IL-6, Collagen-1, and Collagen-3 were higher in the db/db mice than in the WT mice. Infarction increased these levels in the WT and db/db mice. Lina more than EX attenuated the increase in ASC, NALP3, IL-1β, IL-6, Collagen-1 and Collagen-3, TNFα and IL-1β, and decreased apoptosis, especially in the db/db mice. In vitro experiments showed that Lina, but not EX, attenuated the increase in TLR4 expression, an effect that was dependent on p38 activation with downstream upregulation of Let-7i and miR-146b levels. Lina and EX had similar effects on IS and post-infarction function, but Lina attenuated the activation of the inflammasome and the upregulation of collagen-1 and collagen-3 more than direct GLP-1 receptor activation. This effect depends on p38 activation with downstream upregulation of miR-146b levels that suppresses TLR4 expression.
journal_name
Basic Res Cardioljournal_title
Basic research in cardiologyauthors
Birnbaum Y,Tran D,Bajaj M,Ye Ydoi
10.1007/s00395-019-0743-0subject
Has Abstractpub_date
2019-08-06 00:00:00pages
35issue
5eissn
0300-8428issn
1435-1803pii
10.1007/s00395-019-0743-0journal_volume
114pub_type
杂志文章abstract::Using an isolated rat heart preparation (Langendorff perfusion, perfusion pressure 100 cm H2O) the response of the hypertrophied heart (spontaneous hypertensive rats lv/bw ratio 3.6 +/- 0.5) to global normothermic (30 min) and hypothermic (25 degrees C, 120 min) ischemic and cardioplegic arrest and reperfusion (30 min...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/978-3-662-11374-5_12
更新日期:1986-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907360
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journal_title:Basic research in cardiology
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doi:10.1007/s00395-009-0071-x
更新日期:2010-05-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01905508
更新日期:1975-05-01 00:00:00
abstract::Our understanding of what constitutes "normal" collagen organization in wound healing after myocardial injury and how such organization is achieved is still in its infancy. However, once this knowledge has been obtained, it may suggest methods of enhancing or even optimizing healing, and thus provide us with the possi...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950050201
更新日期:1998-01-01 00:00:00
abstract::Mobilization of triacylglycerol stored in heart cells is accomplished by the combined action of lysosomal (acid) lipase and microsomal monoacylglycerol lipase or carboxylesterase. Non(heparin)-releasable neutral or alkaline lipase is similar to non(readily)-releasable lipoprotein lipase (LPL). The enzyme is mainly loc...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01908026
更新日期:1984-05-01 00:00:00
abstract::A survey was made of vagal afferents whose endings originated in cardiopulmonary areas of the Rhesus monkey. Recordings of action potentials from single fiber preparations of the left cervical vagus were made in both open and closed chest monkeys. A total of 425 receptors were identified in sixteen animals. These cons...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02023598
更新日期:1977-07-01 00:00:00
abstract::Denervation deprives the heart of its normal adrenergic and cholinergic control via the sympathetic and parasympathetic pathways. In a heart which is blood supplied by a donor animal of the same species, normal contractility is maintained, probably by blood borne catecholamines or possibly by unknown inotropic agents ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907778
更新日期:1976-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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更新日期:2011-05-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-004-0498-4
更新日期:2005-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
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更新日期:2020-01-09 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907015
更新日期:1990-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s00395-014-0454-5
更新日期:2015-01-01 00:00:00
abstract::Total global ischaemia of the normothermic working rat heart caused an initial positive inotropic response characterized by vigorous contractions. After +/- 15 s this response reached a peak whereafter the isotonic contraction amplitude started to decline. After +/- 3.5 min the heart ceased to beat. The low level of h...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906862
更新日期:1987-05-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-016-0578-x
更新日期:2016-09-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907923
更新日期:1989-03-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950170042
更新日期:2001-07-01 00:00:00
abstract:OBJECTIVE:The clinical usefulness of class III antiarrhythmic drugs for the treatment of tachyarrhythmias is limited by their potential proarrhythmic effects, mainly torsades-depointes (TdP). The goal of this experimental study was to develop an isolated whole-heart model exhibiting typical characteristics of class III...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s003950050073
更新日期:1998-04-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907029
更新日期:1987-07-01 00:00:00
abstract::This study aimed to analyze the role of endothelial progenitor cell (EPC)-derived angiogenic factors and chemokines in the multistep process driving angiogenesis with a focus on the recently discovered macrophage migration inhibitory factor (MIF)/chemokine receptor axis. Primary murine and murine embryonic EPCs (eEPCs...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/s00395-012-0310-4
更新日期:2013-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF00788726
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01907227
更新日期:1987-11-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF02005337
更新日期:1982-07-01 00:00:00
abstract::Transformation of structural, functional, metabolic and molecular characteristics is induced by stimulating fast-twitch muscles with the frequency pattern of a motoneuron normally innervating a slow-twitch muscle. These changes correspond to a transition of a "fast-white" into a "slow-red" muscle. Intermittent stimula...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906369
更新日期:1977-03-01 00:00:00
abstract::To study the signaling mechanisms which mediate ventricular hypertrophy, we utilized the induction of the ANF gene as a marker of the hypertrophic response. The induction of the atrial natriuretic factor gene (ANF) is one of the most conserved features of ventricular hypertrophy, occurring in multiple species (mouse, ...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/978-3-642-72477-0_5
更新日期:1992-01-01 00:00:00
abstract::Cardiac excitation-contraction (EC) coupling consumes vast amounts of cellular energy, most of which is produced in mitochondria by oxidative phosphorylation. In order to adapt the constantly varying workload of the heart to energy supply, tight coupling mechanisms are essential to maintain cellular pools of ATP, phos...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s00395-007-0666-z
更新日期:2007-09-01 00:00:00
abstract::In the newborn several situations of hyperinsulinism can be associated with myocardial hypertrophy and increased contractility. Insulin and the insulin-like growth factors (IGF) are derived from a common ancestral molecule. Insulin exerts mainly metabolic action, whereas the IGFs promote cell multiplication and differ...
journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:10.1007/BF01906959
更新日期:1988-11-01 00:00:00
abstract::Beta-blockers have been shown to reduce the risk of coronary events and reduce the mortality of patients with hypertension and in those who have had a myocardial infarction. Furthermore, the evidence for long-term benefits in these two patient groups are much more convincing for beta-blockers than for other therapeuti...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950070006
更新日期:2000-01-01 00:00:00
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journal_title:Basic research in cardiology
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::In the human heart several isoforms of the sodium pump (Na,K-ATPase, the cardiac glycoside receptor) are expressed (alpha1beta1, alpha2beta1, and alpha3beta1). Their expression is regulated in a highly specific manner, so that there are region specific differences in the expression pattern. The isoform expression patt...
journal_title:Basic research in cardiology
pub_type: 杂志文章,评审
doi:10.1007/s003950200025
更新日期:2002-01-01 00:00:00