Abstract:
AIMS:AMP-activated protein kinase (AMPK) is thought to be a central player in regulating myocardial metabolism and its activation has been shown to inhibit cardiac hypertrophy. Recently, mice with muscle-specific deletion of AMPK β1/β2 subunits (AMPKβ1β2-deficient mice, β1β2M-KO) have been generated and possess <10% of normal AMPK activity in muscle. However, how/if dramatic AMPK deficiency alters cardiac metabolism, function, or morphology has not been investigated. Therefore, the aim of this study was to determine whether a significant loss of AMPK activity alters cardiac function, metabolism, and hypertrophy, and whether this may play a role in the pathogenesis of heart failure. METHODS AND RESULTS:β1β2M-KO mice exhibit an approximate 25% reduction in systolic and diastolic function compared with wild-type (WT) littermates. Despite the well-documented role of AMPK in controlling myocardial energy metabolism, there was no difference in basal glucose and fatty acid oxidation rates between β1β2M-KO and WT mice. However, there was reduced AMPK-mediated phosphorylation of troponin I in β1β2M-KO and reduced ventricular cell shortening in the presence of low Ca(2+), which may explain the impaired cardiac function in these mice. Interestingly, β1β2M-KO mice did not display any signs of compensatory cardiac hypertrophy, which could be attributed to impaired activation of p38 MAPK. CONCLUSIONS:β1β2M-KO mice display evidence of dilated cardiomyopathy. This is the first mouse model of AMPK deficiency that demonstrates cardiac dysfunction in the absence of pathological stress and provides insights into the role of AMPK in regulating myocardial function, metabolism, hypertrophy, and the progression to heart failure.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Sung MM,Zordoky BN,Bujak AL,Lally JS,Fung D,Young ME,Horman S,Miller EJ,Light PE,Kemp BE,Steinberg GR,Dyck JRdoi
10.1093/cvr/cvv166subject
Has Abstractpub_date
2015-07-15 00:00:00pages
235-45issue
2eissn
0008-6363issn
1755-3245pii
cvv166journal_volume
107pub_type
杂志文章abstract:OBJECTIVE:To examine if adenosine prevents oxidant-induced mitochondrial dysfunction by producing nitric oxide (NO) in cardiomyocytes. METHODS AND RESULTS:Adenosine significantly enhanced the fluorescence of DAF-FM, a dye specific for NO, implying that adenosine induces synthesis of NO. Adenosine-induced NO production...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.12.004
更新日期:2005-03-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine if prostaglandin like activity might be involved in changes due to exercise training in the coronary flow responses to hypoxia. DESIGN:The coronary flow response to hypoxia was measured under constant perfusion pressure in isolated perfused hearts from 12 endurance exercise tra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.9.733
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVE:The multifunctional Ca2+-binding protein S100A4 (also known as Mts1 and Fsp1) is involved in fibrosis and tissue remodeling in several diseases including cancer, kidney fibrosis, central nervous system injury, and pulmonary vascular disease. We previously reported that S100A4 mRNA expression was increased in ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2007.03.027
更新日期:2007-07-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00143-0
更新日期:1997-10-01 00:00:00
abstract::Hyponatremia is a frequent electrolyte disorder. It is often found in congestive cardiac failure, liver cirrhosis, plasma volume contraction and in SiADH. In these disorders hyponatremia is caused by nonosmotic vasopressin and sustained fluid intake. This provides a rationale for V2 vasopressin receptor antagonists in...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00288-7
更新日期:2001-08-15 00:00:00
abstract::The significance of pre-existing coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion was studied in anaesthetised open-chest dogs. The extent of myocardial ischaemic damage was assessed by the accumulation of calcium in the central zone of the ischaemic area and the size o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/14.5.288
更新日期:1980-05-01 00:00:00
abstract:AIMS:The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cycli...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr280
更新日期:2012-01-01 00:00:00
abstract::Infarct size can be limited by reducing the determinants of infarct size or increasing collateral blood flow by treatment initiated before the ischaemic event. Reperfusion is the definitive treatment for permanently reducing infarct size and restoring some degree of contractile function to the affected myocardium. Inn...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp129
更新日期:2009-07-15 00:00:00
abstract:AIMS:In developing blood vessel networks, the overall level of vessel branching often correlates with angiogenic sprout initiations, but in some pathological situations, increased sprout initiations paradoxically lead to reduced vessel branching and impaired vascular function. We examine the hypothesis that defects in ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw091
更新日期:2016-07-01 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is a major risk factor for cardio-embolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern. This study sought to identify new targets to develop safer antithrombotic therapie...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw049
更新日期:2016-06-01 00:00:00
abstract:AIMS:The molecular mechanisms controlling heart function and rhythmicity are incompletely understood. While it is widely accepted that the type 2 ryanodine receptor (Ryr2) is the major Ca(2+) release channel in excitation-contraction coupling, the role of these channels in setting a consistent beating rate remains cont...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs260
更新日期:2012-12-01 00:00:00
abstract:OBJECTIVES:To investigate the effect of alpha,beta(1) and beta(2) adrenergic receptor (AR) stimulation on coronary hemodynamics, myocardial oxygen consumption (M(v)O(2)) and metabolic substrate preference in advanced dilated cardiomyopathy (DCM). METHODS:We studied 19 conscious, instrumented dogs with pacing-induced D...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00490-4
更新日期:2002-02-01 00:00:00
abstract:Aims:Hypertensive cardiac hypertrophy is associated with reduced coronary flow reserve, but its impact on coronary flow regulation and vasomotor function remains incompletely understood and requires further investigation. Methods and results:Left ventricular hypertrophy was induced in mice by transverse aortic coarcta...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvx103
更新日期:2017-09-01 00:00:00
abstract::Matricellular proteins are extracellular matrix proteins that modulate cell-matrix interactions and cell function, and do not seem to have a direct structural role. The family includes tenascin-C (TN-C), tenascin-X (TN-X), osteonectin, osteopontin, thrombospondin-1 (TSP1) and thrombospondin-2 (TSP2). Expression of mat...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.06.006
更新日期:2004-10-01 00:00:00
abstract::The effect of chronic propranolol administration (2 mg.kg-1.d-1 for 14d) and withdrawal on microvascular perfusion was studied in rabbit myocardium. Fluorescein isothiocyanate-dextran was injected into four groups of anaesthetised open chest rabbits. Fluorescent microscopy was used to identify the perfused vessels and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.11.793
更新日期:1988-11-01 00:00:00
abstract:OBJECTIVE:Transient atrial fibrillation is sometimes observed following adenosine administration and adenosine is known to shorten atrial action potential duration and refractory period. This study was designed to characterise the dose-response relationship of adenosine on these variables relative to arrhythmia inducti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.9.1385
更新日期:1994-09-01 00:00:00
abstract:AIMS:Arrhythmias and sudden cardiac death (SCD) occur commonly in patients with heart failure. We found T-box 5 (TBX5) dysregulated in ventricular myocardium from heart failure patients and thus we hypothesized that TBX5 reduction contributes to arrhythmia development in these patients. To understand the underlying mec...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa239
更新日期:2020-08-10 00:00:00
abstract:AIMS:Doxorubicin (DOX) is widely used in cytostatic treatments, although it may cause cardiovascular dysfunction as a side effect. DOX treatment leads to enhanced free radical production that in turn causes DNA strand breakage culminating in poly(ADP-ribose) polymerase (PARP) activation and mitochondrial and cellular d...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr246
更新日期:2011-12-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to evaluate the protective effect of verapamil during myocardial ischaemia and reperfusion. DESIGN:In vivo phosphorus-31 (31P) magnetic resonance spectroscopy was performed on rats pretreated with verapamil (mg.kg-1 intraperitoneal) and controls during a 45 min left coronary artery occlusio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.2.101
更新日期:1991-02-01 00:00:00
abstract::The theory related to the loss of R waves and appearance of Q waves in acute myocardial infarction is discussed. A method of praecordial mapping of RS ratio changes and the appearance of Q waves that occur in acute myocardial infarction is described. The serial changes in these electrocardiographic signs in 17 patient...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.2.167
更新日期:1977-03-01 00:00:00
abstract:OBJECTIVE:Chlamydia pneumoniae infection has been associated with atherosclerosis, although the mechanisms by which C. pneumoniae contribute to atherogenesis remain unclear. Altered production of nitric oxide, a known bactericidal and anti-inflammatory agent, represents one possible mechanistic link. To examine this is...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00389-4
更新日期:2003-10-15 00:00:00
abstract::Changes in left ventricular internal diameter resulting from increasing intrapericardial pressure induced by increasing the pericardial fluid volume were studied in closed chest, anaesthetized dogs. Left ventricular internal diameters were measured by placing an ultrasonic dimension catheter in the left ventricle at t...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.6.707
更新日期:1975-11-01 00:00:00
abstract::The most critical determinant of prognosis in patients with acute myocardial infarction (MI) is infarct magnitude, which can be established within several hours of an attack. The importance of the subsequent healing process is not negligible, however. In fact, much experimental and clinical evidence suggests that late...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp032
更新日期:2009-07-15 00:00:00
abstract:OBJECTIVE:The aim was to determine the ionic basis of action potential lengthening associated with cardiac hypertrophy. METHODS:Action potentials and ionic currents of left ventricular myocytes isolated from normal and hypertrophied hearts were recorded with patch pipettes. Since cardiac hypertrophy is a time dependen...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.8.1180
更新日期:1994-08-01 00:00:00
abstract::We tested the hypothesis that visualisation of defects on thallium-201 (201Tl) myocardial perfusion images (MPI) depends on the duration of the ischaemic state between 201Tl injection and the time of reperfusion of an occluded coronary artery. Praecordial imaging with a gamma camera was performed in 24 anaesthetised, ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.1.47
更新日期:1982-01-01 00:00:00
abstract::To determine the effect of an anteroseptal myocardial infarction on right ventricular systolic and diastolic function, we studied 12 pigs before and 1 h after left anterior descending coronary artery occlusion. Total arterial occlusion was achieved by the percutaneous, transcatheter placement of a 1 mm Teflon plug int...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.1.46
更新日期:1989-01-01 00:00:00
abstract:OBJECTIVE:Pericytes, located in close proximity to the underlying endothelium, form an integral component of the microvasculature. These cells are intimately involved in angiogenesis, which is of fundamental importance in many physiological and pathological processes. We evaluated the influence of pericyte-conditioned ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.08.003
更新日期:2006-01-01 00:00:00
abstract:OBJECTIVE:Cholinergic vasodilation has been thought to play little if any role in the regulation of blood pressure in humans. Autonomic denervation potentiates the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but the mechanism is unclear. We hypothesized that this may be related to loss of neu...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1016/s0008-6363(01)00325-x
更新日期:2001-09-01 00:00:00
abstract::The structural basis for the development of congestive heart failure (CHF) is a maladaptive myocardial remodeling process which occurs secondarily to post-myocardial infarction (MI), hypertensive hypertrophy, or cardiomyopathy. Both cellular and extracellular factors are involved in the remodeling process and it is th...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2005.10.004
更新日期:2006-02-15 00:00:00
abstract:OBJECTIVE:Polymorphonuclear leukocytes (PMN), retained in the microvascular bed, can contribute to postischemic myocardial reperfusion injury. Since a beneficial effect of ACE-inhibition on reperfusion injury has been reported, we investigated the impact of cilazaprilat on PMN dependent reperfusion injury in isolated g...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00191-0
更新日期:1997-12-01 00:00:00