Abstract:
AIMS:Cardiac hypertrophy is characterized by a shift in metabolic substrate utilization, but the molecular events underlying the metabolic remodelling remain poorly understood. We explored metabolic remodelling and mitochondrial dysfunction in cardiac hypertrophy and investigated the cardioprotective effects of choline. METHODS AND RESULTS:The experiments were conducted using a model of ventricular hypertrophy by partially banding the abdominal aorta of Sprague Dawley rats. Cardiomyocyte size and cardiac fibrosis were significantly increased in hypertrophic hearts. In vitro cardiomyocyte hypertrophy was induced by exposing neonatal rat cardiomyocytes to angiotensin II (Ang II) (10-6 M, 24 h). Choline attenuated the mito-nuclear protein imbalance and activated the mitochondrial-unfolded protein response (UPRmt) in the heart, thereby preserving the ultrastructure and function of mitochondria in the context of cardiac hypertrophy. Moreover, choline inhibited myocardial metabolic dysfunction by promoting the expression of proteins involved in ketone body and fatty acid metabolism in response to pressure overload, accompanied by the activation of sirtuin 3/AMP-activated protein kinase (SIRT3-AMPK) signalling. In vitro analyses demonstrated that SIRT3 siRNA diminished choline-mediated activation of ketone body metabolism and UPRmt, as well as inhibition of hypertrophic signals. Intriguingly, serum from choline-treated abdominal aorta banding models (where β-hydroxybutyrate was increased) attenuated Ang II-induced myocyte hypertrophy, which indicates that β-hydroxybutyrate is important for the cardioprotective effects of choline. CONCLUSION:Choline attenuated cardiac dysfunction by modulating the expression of proteins involved in ketone body and fatty acid metabolism, and induction of UPRmt; this was likely mediated by activation of the SIRT3-AMPK pathway. Taken together, these results identify SIRT3-AMPK as a key cardiac transcriptional regulator that helps orchestrate an adaptive metabolic response to cardiac stress. Choline treatment may represent a new therapeutic strategy for optimizing myocardial metabolism in the context of hypertrophy and heart failure.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Xu M,Xue RQ,Lu Y,Yong SY,Wu Q,Cui YL,Zuo XT,Yu XJ,Zhao M,Zang WJdoi
10.1093/cvr/cvy217subject
Has Abstractpub_date
2019-03-01 00:00:00pages
530-545issue
3eissn
0008-6363issn
1755-3245pii
5079903journal_volume
115pub_type
杂志文章abstract:AIMS:We investigated the molecular mechanism of rapid-depolarization-induced atrial fibrosis. METHODS AND RESULTS:We used a direct atrial myocyte-fibroblast contact co-culture and a fibroblast-specific transforming growth factor β1 (TGF-β1), connective tissue growth factor (CTGF) and procollagen type I α-1 (COL1A1) lu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq322
更新日期:2011-03-01 00:00:00
abstract::Known viable allograft canine pulmonary valves were inserted in an isotopic position ensuring normal physiological function and simulating the clinical situation. Valves removed at periods up to eight weeks were assessed for viability using previously established criteria of tissue culture and protein and collagen syn...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.1.78
更新日期:1977-01-01 00:00:00
abstract:OBJECTIVE:The purpose was to investigate the influence of the 38-amino-acid neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP38), on contractile function and coronary vascular tone in neonatal hearts. METHODS:Isolated, paced (150 bpm), isovolumically-beating, piglet hearts (n = 19) underwent retr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Papillary muscles isolated from the left ventricle of 17-20 day old Syrian hamsters with genetic cardiomyopathy (BIO 14.6 strain) were examined for their mechanophysiological response to the beta adrenoceptor agonist isoprenaline. The indices of isometric twitch for both myopathic and aged matched normal (BIO RB strai...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.8.609
更新日期:1986-08-01 00:00:00
abstract:OBJECTIVE:The adhesive interaction of monocytes and endothelial cells has been implicated as a regulatory signal in the cell activation that is involved in the pathogenesis of atherosclerosis. We investigated the effect of monocyte-endothelial cell interaction on the expression of adhesion molecules, intercellular adhe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00085-5
更新日期:1996-08-01 00:00:00
abstract::An in situ preparation of the rabbit thoracic aorta has been used to study the transport of short-lived radioactive isotopes of oxygen (15O16O), nitrogen (13N14N) and an isotope of xenon (133Xe) from 0.9% NaCl into the artery wall. At a luminal hydrostatic pressure of 2 kPa the uptake of all three isotopes by the inti...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/15.8.456
更新日期:1981-08-01 00:00:00
abstract::Atherosclerosis is considered a to be multifactorial disease driven by inflammatory reactions. The process of inflammation also contributes to the pathogenesis of acute atherothrombotic events. C-reactive protein (CRP) is an acute phase protein and its concentration in serum reflects the inflammatory condition of the ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.03.004
更新日期:2006-07-01 00:00:00
abstract:AIMS:Adequate microcirculatory perfusion, and not just opening of occluded arteries, is critical to salvage heart tissue following myocardial infarction. However, the degree of microvascular perfusion taking place is not known, limited primarily by an inability to directly image coronary microcirculation in a beating h...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz118
更新日期:2019-11-01 00:00:00
abstract:OBJECTIVE:Jervell and Lange-Nielsen syndrome (JLNS) is a recessively inherited long QT syndrome (LQTS) characterised by profound sensorineural deafness and predisposition to syncope and sudden cardiac death. Mutation analysis has established the presence of mutations in affected individuals in the genes KCNQ1 and KCNE1...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00350-9
更新日期:2001-09-01 00:00:00
abstract:OBJECTIVE:Angiotensin II stimulates vascular smooth muscle cell (VSMC) growth, and is considered to be an important mediator of intimal thickening after vascular injury. Recent evidence has indicated that VSMC apoptosis plays a major role in the response to balloon injury, and we therefore examined the effect of angiot...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00265-5
更新日期:2000-02-01 00:00:00
abstract:OBJECTIVES:The contribution of vascular changes to the development of heart failure is largely unknown. In the present study, we evaluated endothelial and vascular contractile function in the rat hindlimb vascular bed after myocardial infarction (MI), including the modulatory role of basal nitric oxide (NO) production ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00147-9
更新日期:1999-08-15 00:00:00
abstract:OBJECTIVE:It has been proposed that human immunodeficiency virus (HIV) infection-induced inflammatory environment may contribute to the pathogenesis of cardiovascular diseases. Recent studies have also demonstrated the potential role of estrogen as therapeutic agents in the prevention or treatment of cardiovascular dis...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.03.006
更新日期:2004-07-01 00:00:00
abstract:AIMS:In mammalian ventricles, electrical gradients establish electrical heterogeneities as essential tissue mechanisms to optimize mechanical efficiency and safeguard electrical stability. Electrical gradients shape mammalian electrocardiographic patterns; disturbance of electrical gradients is proarrhythmic. The zebra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa238
更新日期:2020-07-31 00:00:00
abstract::Rupture of vulnerable atherosclerotic plaques leading to an atherothrombotic event is the primary driver of myocardial infarction and stroke. The ability to detect non-invasively the presence and evolution of vulnerable plaques could have a huge impact on the future identification and management of atherosclerotic car...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvz162
更新日期:2019-12-01 00:00:00
abstract::The cardiospecificity of the MB isoenzyme of creatine kinase, EC 2.7.3.2, (CK) with its associated diagnostic and research value has resulted in the development of a number of procedures for the separation and quantitation of the three isoenzymes of CK. In our experience methods involving cellulose acetate electrophor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.2.94
更新日期:1977-03-01 00:00:00
abstract:OBJECTIVES:Responses to EDHF are usually characterised in the presence of nitric oxide synthase (NOS) and cyclooxygenase (COX) inhibitors. The contribution of NO to endothelium-dependent relaxation in the presence of NOS inhibitors was assessed using NO scavengers with the objective of testing (i) whether any residual ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00611-9
更新日期:2003-01-01 00:00:00
abstract:OBJECTIVE:The aims were (1) to investigate the effect of hypertention on left ventricular dilatation and haemodynamic alterations following acute myocardial infarction in spontaneously hypertensive rats (SHR) and normotensive rats (WKY); (2) to compare haemodynamic indices between the two groups; (3) to assess whether ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract:AIMS:Sphingosine-1-phosphate (S1P), a key regulator of vascular homeostasis and angiogenesis, promotes endothelial cell migration via stimulation of phosphoinositide 3-kinase (PI3K). The aim of this study was to identify the role of PI3Kbeta and gamma isoforms and their downstream effector pathways in mediating endothe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn159
更新日期:2008-10-01 00:00:00
abstract:AIMS:Extracellular nucleotides are vasoactive molecules. The concentrations of these molecules are regulated by ectonucleotidases. In this study, we investigated the role of the blood vessel ectonucleotidase NTPDase1, in the vasoconstrictor effect of nucleotides using Entpd1(-/-) mice. METHODS AND RESULTS:Immunofluore...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp265
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVE:To determine the effect of Na(+)-H+ exchange blockade on ischemic rigor contracture and reperfusion-induced hypercontracture. METHODS:Thirty-six pigs were submitted to 55 min of coronary occlusion and 5 h reperfusion. Myocardial segment length analysis with ultrasonic microcrystals was used to detect ischemi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00106-5
更新日期:1997-07-01 00:00:00
abstract:OBJECTIVE:Acute ischemia comes with two phases of life-threatening arrhythmias, early (within 10 minutes, 1A) and late (after about 15 minutes, 1B). The mechanism of the latter is unknown and in this paper, we test the hypothesis that a phase of intermediate coupling between surviving epicardium and inexcitable midmyoc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00222-x
更新日期:2001-05-01 00:00:00
abstract::Therapeutic neovascularization for cardiovascular ischemia is a promising avenue in spite of disappointing early clinical trial results. The concept of three different mechanisms of neovascularization has served to define potential therapeutic targets such as vascular remodeling and stem cell recruitment, but it is an...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.11.020
更新日期:2005-02-15 00:00:00
abstract:OBJECTIVES:Anthracyclines cause apoptotic death in many cell types through activation of the ceramide pathway. We tested the hypothesis that doxorubicin induces cardiac myocyte apoptosis through ceramide generation. METHODS:Adult rat ventricular myocytes were grown in the presence of 10% fetal calf serum, and exposed ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00142-x
更新日期:1999-08-01 00:00:00
abstract::The major limitation to antiarrhythmic drug therapy is the risk of arrhythmia promotion, or 'proarrhythmia.' This complication may be lethal, and greatly restricts the value of antiarrhythmic agents, particularly for arrhythmias without an intrinsic mortality risk, such as atrial fibrillation. In order for improved an...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00293-9
更新日期:1998-03-01 00:00:00
abstract:AIMS:Although the use of drug-eluting stents (DESs) has been shown to limit neointima hyperplasia, currently available DESs may adversely affect re-endothelialization. To evaluate whether a novel gene silencer pyrrole-imidazole (PI) polyamide targeting transforming growth factor (TGF)-beta1 is a candidate agent for the...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn355
更新日期:2009-03-01 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:AIMS:Pulmonary arterial endothelial cells (PAECs) express the enzymes needed for generation of l-arginine from intracellular l-citrulline but do not express the enzymes needed for de novo l-citrulline synthesis. Hence, l-citrulline levels in PAECs are dependent on l-citrulline transport. Once generated, l-arginine can ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs186
更新日期:2012-08-01 00:00:00
abstract::Although fully explored in larger animals, the role of injection site and sample microsphere content on variability of coronary blood flow (CBF) measurement using the microsphere technique remains controversial in rats despite the fact that this species is extensively used in cardiovascular research. We therefore inve...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.5.443
更新日期:1989-05-01 00:00:00
abstract::To investigate cardiovascular changes in experimental acromegaly, a growth hormone-secreting tumour (MtT-W-15) was implanted in adult female rats. Somatic and tumour growth occurred steadily during the 8 week study period, as did an increase in serum growth hormone titre. Weight of left ventricle and right ventricle i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.5.270
更新日期:1985-05-01 00:00:00
abstract:OBJECTIVES:5-Hydroxytryptamine (5-HT) has a wide range of vascular effects mediated via specific receptors and it has been suggested to be a mediator in ischemic heart disease. The aim of the present study was to localise the 5-HT receptors within the vessel wall. METHODS:Epicardial coronary arteries obtained from pat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00029-6
更新日期:1996-05-01 00:00:00