Abstract:
:One of the obstacles to a better understanding of the pathogenesis of human cardiomyopathies has been poor availability of heart-tissue samples at early stages of disease development. This has possibly changed by the advent of patient-derived induced pluripotent stem cell (hiPSC) from which cardiomyocytes can be derived in vitro. The main promise of hiPSC technology is that by capturing the effects of thousands of individual gene variants, the phenotype of differentiated derivatives of these cells will provide more information on a particular disease than simple genotyping. This article summarizes what is known about the 'human cardiomyopathy or heart failure phenotype in vitro', which constitutes the reference for modelling sarcomeric cardiomyopathies in hiPSC-derived cardiomyocytes. The current techniques for hiPSC generation and cardiac myocyte differentiation are briefly reviewed and the few published reports of hiPSC models of sarcomeric cardiomyopathies described. A discussion of promises and challenges of hiPSC-modelling of sarcomeric cardiomyopathies and individualized approaches is followed by a number of questions that, in the view of the authors, need to be answered before the true potential of this technology can be evaluated.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Eschenhagen T,Mummery C,Knollmann BCdoi
10.1093/cvr/cvv017subject
Has Abstractpub_date
2015-04-01 00:00:00pages
424-38issue
4eissn
0008-6363issn
1755-3245pii
cvv017journal_volume
105pub_type
杂志文章,评审abstract::The response of a simple systolic time interval, the interval between the Q wave and the onset of the aortic blood pressure pulse (the QA interval), to changes in cardiac contractility, cardiac loading, and heart rate was evaluated in anaesthetised open chest dogs. The QA interval was found to be sensitive to increase...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.6.444
更新日期:1986-06-01 00:00:00
abstract::Primary cardiomyopathy is an important cause of mortality in children and adults. Apart from inherited disorders of myocardial contractile and structural proteins, several defects of energy metabolism may cause cardiomyopathy. Most of the energy required for myocardial contraction is derived from aerobic metabolism. F...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00141-7
更新日期:1997-08-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to investigate observed differences in beta adrenergic and apparent non-beta-adrenergic binding of (-)[125I]-iodocyanopindolol (125I-ICYP). DESIGN:Binding parameters for several beta adrenergic agonists and antagonists were examined in radioligand binding assay, using 125I-ICYP as radioliga...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/25.9.764
更新日期:1991-09-01 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:Aims:MicroRNAs (miRNAs) have been implicated in the pathogenesis of pulmonary hypertension (PH), a multifactorial and progressive condition associated with an increased afterload of the right ventricle leading to heart failure and death. The main aim of this study was to correlate the levels of miR-424(322) with the se...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvx187
更新日期:2018-01-01 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:Shock wave therapy (SWT) represents a clinically widely used angiogenic and thus regenerative approach for the treatment of ischaemic heart or limb disease. Despite promising results in preclinical and clinical trials, the exact mechanism of action remains unknown. Toll-like receptor 3, which is part of the innate...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv272
更新日期:2016-02-01 00:00:00
abstract:OBJECTIVES:To investigate the role of ventricular and atrial beta-adrenoceptor activation by isoprenaline in the genesis of rhythm disorders and risk of fibrillation in the healthy or ischaemic heart. METHODS:The study was performed in anaesthetized, open-chest pigs. Electrical fibrillation threshold (EFT) of the vent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(96)00156-3
更新日期:1996-12-01 00:00:00
abstract::A diminished sympathetic activity has been related to training bradycardia seen at rest and during exercise. In order to evaluate if changes in heart adrenergic receptors can be one of the mechanisms by which the sympathetic responsiveness could be decreased by physical training, the number and affinity of beta-adrene...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/16.9.530
更新日期:1982-09-01 00:00:00
abstract:OBJECTIVE:Heart failure is associated with reduced function of sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) but increased function of sarcolemmal Na+/Ca2+ exchanger (NCX), leading to decreased SR Ca2+ content and loss of frequency-potentiation of contractile force. We reported that SERCA2a-overexpression in transg...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.006
更新日期:2005-09-01 00:00:00
abstract:OBJECTIVE:The function of angiotensin converting enzyme (ACE) at cell sites of high collagen turnover, such as heart valves, is uncertain. The aim of this study was to assess ACE and kininase-II-like activities and collagen turnover in cultured valvular interstitial cells of the adult rat heart. METHODS:The valvular i...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract:ABSTRACT:Sepsis accounts for nearly 700 000 deaths in Europe annually and is caused by an overwhelming host response to infection resulting in organ failure. The endothelium is an active contributor to sepsis and as such represents a major target for therapy. During sepsis, endothelial cells amplify the immune response...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa070
更新日期:2021-01-01 00:00:00
abstract:AIMS:Both cyclooxygenase-2 (COX-2) and the transcription factor signal transducer and activator of transcription 3 (Stat3) are involved in adaptive growth and survival of cardiomyocytes. In ventricular cardiomyocytes, prostaglandin E(2) (PGE(2)), a major COX-2 product, leads to adaptive growth via Stat3 activation, but...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn171
更新日期:2008-10-01 00:00:00
abstract:AIMS:GATA4 is a transcription factor that is up-regulated during cardiac hypertrophy and plays a fundamental role in myocyte growth and survival. In this study, we investigate the transcriptional vs. post-transcriptional mechanisms that are involved in regulating GATA4 in the heart during neonatal and pressure overload...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs001
更新日期:2012-03-15 00:00:00
abstract:OBJECTIVES:Age-related medial calcification (elastocalcinosis) of large arteries is accelerated in diabetes and appears mainly in distal arteries. The aim was to devise a rat model of elastocalcinosis in association with diabetes to examine the hypothesis that diabetes accelerates vascular calcification experimentally....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.11.001
更新日期:2007-02-01 00:00:00
abstract:AIMS:Melusin is a muscle-specific chaperone protein whose expression is required for a compensatory hypertrophy response to pressure overload. Here, we evaluated the consequences of melusin overexpression in the setting of myocardial infarction (MI) using a comprehensive multicentre approach. METHODS AND RESULTS:Mice ...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt235
更新日期:2014-01-01 00:00:00
abstract:AIMS:Thromboxane A2 (TXA2) induces platelet adhesion through thromboxane prostanoid (TP) receptor. Platelets contain many pro-angiogenic factors and are recruited to the site of vascular injury. However, the cellular and molecular mechanisms of platelet-dependent angiogenesis, especially the involvement of TP signallin...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv139
更新日期:2015-09-01 00:00:00
abstract:AIMS:The risk of mortality from the coronavirus disease that emerged in 2019 (COVID-19) is increased by comorbidity from cardiovascular and pulmonary diseases. Air pollution also causes excess mortality from these conditions. Analysis of the first severe acute respiratory syndrome coronavirus (SARS-CoV-1) outcomes in 2...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa288
更新日期:2020-12-01 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:AIMS:n-3 Polyunsaturated fatty acids (PUFAs) are known to protect the cardiovascular system and improve blood pressure control. These important dietary constituents are converted into bioactive metabolites, but their role in regulation of the cardiovascular system is unclear. In particular, the functions of the cytochr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq411
更新日期:2011-05-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate whether infusion of either atrial natriuretic factor (ANF, 800 ng.h-1.rat-1) or a specific inhibitory of neutral endopeptidase 24.11 (NEI, UK 73,967, 5.4 mg.kg-1.d-1) can influence the reversal of the pulmonary vascular remodelling produced by exposure to hypoxia. METHODS:Male Wist...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.4.519
更新日期:1994-04-01 00:00:00
abstract:OBJECTIVE:Smooth muscle cell proliferation and migration are the predominant responses to intimal and medial injury after percutaneous transluminal coronary angioplasty. The in vivo inhibitory effect of heparin on these responses is well documented. To test the hypothesis that the antiproliferative effect of heparin in...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.7.1209
更新日期:1993-07-01 00:00:00
abstract:OBJECTIVE:Evidence suggests important relationships among chronic inflammatory processes, endothelial dysfunction, hypertension and target organ damage. The present study examined the effects of chronic treatment with an anti-inflammatory p38 mitogen-activated protein kinase (MAPK) inhibitor (SB-239063AN) in the N(omeg...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.12.021
更新日期:2005-04-01 00:00:00
abstract:OBJECTIVE:The aim was to study the effect of thyroid hormone on collagen gene expression in the myocardium of the tight skin mouse (TSK), a genetic model of myocardial fibrosis. METHODS:Heterozygous male (TSK/+) (n = 20) and normal (+/+) homozygous mice (n = 20), 1.5-2 months old of the C57 BL/6 strain were studied. V...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.6.603
更新日期:1992-06-01 00:00:00
abstract::End tidal PCO2 (PETCO2) has been found to be a good prognostic indicator of successful resuscitation from cardiac arrest. To explore the value of this measurement further, we carried out a series of experiments during cardiac arrest and closed chest resuscitation in 14 mechanically ventilated Sprague-Dawley rats. Vent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.4.364
更新日期:1989-04-01 00:00:00
abstract:BACKGROUND:During reperfusion of ischaemic myocardium, Na+/H+ exchange promotes recovery from acidosis resulting in an accumulation of intracellular Na+. This leads to calcium overload via Na+/Ca2+ exchange and might result in cell necrosis contributing to reperfusion injury. METHODS AND RESULTS:We assessed whether HO...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
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...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy217
更新日期:2019-03-01 00:00:00
abstract::Atrial fibrillation (AF) is the most commonly encountered clinical arrhythmia associated with pronounced morbidity, mortality, and socio-economic burden. This pathological entity is associated with an altered expression profile of genes that are important for atrial function. MicroRNAs (miRNAs), a new class of non-cod...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvq350
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that prolonged physical exercise induces long-lasting effects on blood pressure and heart rate we studied 17 endurance runners before and after the 1995 Sandia Wilderness Crossing Research Run (46 km of rocky trails, average altitude 2500 m). METHODS:We evaluated the response of the ca...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00025-4
更新日期:1997-05-01 00:00:00
abstract:OBJECTIVE:R 75,231, a potent and specific nucleoside transport inhibitor, largely prevents cardiac damage and death in catecholamine challenged rabbits. The major biochemical effect of nucleoside transport inhibition in ischaemic and reperfused myocardium is a prolonged accumulation of adenosine. The cardioprotection b...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.1.111
更新日期:1993-01-01 00:00:00