Abstract:
AIMS:Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capacity and the associated in vivo, cellular and molecular alterations. METHODS AND RESULTS:We evaluated lung and heart viral titers in mice infected with either one of several hIAV strains inoculated intranasally. Three-dimensional reconstructions of infected cardiac tissue were used to identify viral proteins inside mouse cardiomyocytes, Purkinje cells, and cardiac vessels. Viral replication was measured in mouse cultured cardiomyocytes. Human induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) were used to confirm infection and study underlying molecular alterations associated with the in vivo electrophysiological phenotype. Pathogenic and attenuated hIAV strains infected and replicated in cardiomyocytes, Purkinje cells and hiPSC-CMs. The infection was also present in cardiac endothelial cells. Remarkably, lung viral titers did not statistically correlate with viral titers in the mouse heart. The highly pathogenic human recombinant virus PAmut showed faster replication, higher level of inflammatory cytokines in cardiac tissue and higher viral titers in cardiac HL-1 mouse cells and hiPSC-CMs compared with PB2mut attenuated virus. Correspondingly, cardiac conduction alterations were especially pronounced in PAmut-infected mice, associated with high mortality rates, compared with PB2mut-infected animals. Consistently, connexin43 and NaV1.5 expression decreased acutely in hiPSC-CMs infected with PAmut virus. YEM1L protease also decreased more rapidly and to lower levels in PAmut-infected hiPSC-CMs compared with PB2mut-infected cells, consistent with mitochondrial dysfunction. Human IAV infection did not increase myocardial fibrosis at 4 days post-infection, although PAmut-infected mice showed an early increase in mRNAs expression of lysyl oxidase. CONCLUSIONS:Human IAV can infect the heart and cardiac specific conduction system, which may contribute to cardiac complications and premature death. TRANSLATIONAL PERSPECTIVE:Influenza A virus (IAV) can infect several cell types in the mouse heart. Human IAV with the highest pathogenicity replicate more rapidly in mouse cardiomyocyte cultures and induce a cardiac pro-inflammatory state, which correlates with underlying molecular changes and mitochondrial dysfunction in human induced pluripotent stem cells-derived cardiomyocytes. The data demonstrate that heart infection and associated damage need not be a consequence of lung pathology. In fact, direct cardiac pathogenicity with the virus reaching and infecting the heart seems more relevant, which supports the relevance of early detection of IAV in clinical cases with acute cardiac disease during influenza outbreaks.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Filgueiras-Rama D,Vasilijevic J,Jalife J,Noujaim SF,Alfonso JM,Nicolas-Avila JA,Gutierrez C,Zamarreño N,Hidalgo A,Bernabé A,Cop CP,Ponce-Balbuena D,Guerrero-Serna G,Calle D,Desco M,Ruiz-Cabello J,Nieto A,Falcon Adoi
10.1093/cvr/cvaa117subject
Has Abstractpub_date
2020-04-28 00:00:00eissn
0008-6363issn
1755-3245pii
5826367pub_type
杂志文章abstract:AIMS:Ivabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricular assist devices (LVAD), is unknown. The aim of this study was to investigate the effec...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs318
更新日期:2013-02-01 00:00:00
abstract:OBJECTIVE:Calcitonin gene related peptide (CGRP) is a potent vasodilator found in sensory nerve endings in coronary arteries. The effect of intravenous CGRP on myocardial ischaemia, cardiovascular haemodynamics, and epicardial coronary artery stenoses was studied in patients with angina to investigate the possible role...
journal_title:Cardiovascular research
pub_type: 临床试验,杂志文章
doi:10.1093/cvr/27.8.1477
更新日期:1993-08-01 00:00:00
abstract:AIMS:Hypertension is accompanied by structural remodelling of vascular extracellular matrix (ECM). Tissue inhibitor of metalloproteinases (TIMPs) inhibits matrix metalloproteinases (MMPs) that degrade the matrix structural proteins. In response to a hypertensive stimulus, the balance between MMPs and TIMPs is altered. ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt067
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVES:Elevated systemic arterial blood pressure is associated with left ventricular hypertrophy and fibrosis. It has been suggested that both circulating and local myocardial renin-angiotensin systems play a role in mediating these responses. Here we describe the natural history of ventricular hypertrophy and fibr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00063-8
更新日期:2000-07-01 00:00:00
abstract:OBJECTIVE:This study was conducted to evaluate to what extent the ischemia-reperfusion injury resulting from the cardiopulmonary bypass (CPB) and aortic cross-clamping procedures during coronary artery bypass grafting (CABG) contributes to the systemic inflammatory response generally found in these patients. METHODS:S...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00403-4
更新日期:2000-03-01 00:00:00
abstract:AIMS:Levels of circulating CD14(high)CD16(+) monocytes increase in atherosclerotic patients and are predictive of future cardiovascular events. Platelet activation has been identified as a crucial determinant in the acquisition of a CD16(+) phenotype by classical CD14(high)CD16(-) cells. We tested the hypothesis that a...
journal_title:Cardiovascular research
pub_type: 杂志文章,随机对照试验
doi:10.1093/cvr/cvw089
更新日期:2016-07-01 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 structural nature of fibrillar collagen involved in the replacement fibrosis which accompanies discrete areas of cell necrosis remains uncertain, as does its influence on the diastolic and systolic stiffness of the intact myocardium. This study, using 15 micron diameter microsphere embolisation of the rat myocardi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.8.655
更新日期:1989-08-01 00:00:00
abstract:Aims:Circulating proteins larger than 3 nm can be transported across continuous endothelial barrier of blood vessels via transcytosis. However, excessive accumulation of serum proteins within the vessel walls is uncommon even for those abundant in the circulation. The aim of this study was to investigate how transcytos...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy181
更新日期:2019-02-01 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:AIMS:Exercise started early after myocardial infarction (MI) improves in vivo cardiac function and myofilament responsiveness to Ca(2+). We investigated whether this represents partial or complete reversal of cellular remodelling. METHODS AND RESULTS:Mice with MI following left coronary ligation were given free access...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp381
更新日期:2010-04-01 00:00:00
abstract:OBJECTIVE:Diastolic dysfunction is a characteristic finding of the aged mammalian heart. Parvalbumin acts as a Ca2+ sink and enhances relaxation in skeletal muscle, and overexpression of parvalbumin in myocardium increased cardiac relaxation in vitro as well as in vivo. Therefore, the objective of this study is to test...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.06.028
更新日期:2005-05-01 00:00:00
abstract::Felodipine (4(2,3-dichlorophenyl)-1,4-dihydro-2, 6-dimethyl-3-ethoxycarbonyl-5-methoxycarbonyl pyridine)), a selective vasodilating anti-hypertensive drug, was used in the treatment of spontaneously hypertensive rats (SHRs) and age-matched Wistar-Kyoto rats (WKYs) from age 6 to 14 weeks, ie during the time of high blo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.9.528
更新日期:1985-09-01 00:00:00
abstract:OBJECTIVES:The aim was to determine the effect and mechanisms by which myocyte stretch interacts with the prolongation of action potential duration (APD) by the class III antiarrhythmic agent E-4031. METHODS:Action potentials and whole-cell currents were measured in isolated guinea pig ventricular myocytes with a patc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the ventricular/vascular coupling of the intact right heart under conditions of normal operation and acute pulmonary hypertension. METHODS:Right ventricular contractility was obtained by calculating the end systolic pressure-volume relationship (Ees) and the effective pulmonary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.9.839
更新日期:1992-09-01 00:00:00
abstract:OBJECTIVE:The aim was to test the hypothesis that nitric oxide (or a related compound) contributes to the coronary vasodilatation during physiological increases of myocardial O2 consumption that occur with exercise. METHODS:Active hyperaemia associated with graded treadmill exercise and coronary reactive hyperaemia we...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.1.119
更新日期:1994-01-01 00:00:00
abstract:AIMS:A robust inflammatory response to tissue injury is a necessary part of the repair process but the deposition of scar tissue is a direct downstream consequence of this response in many tissues including the heart. Adult zebrafish not only possess the capacity to regenerate lost cardiomyocytes but also to remodel an...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz221
更新日期:2020-06-01 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:BACKGROUND:A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvt269
更新日期:2014-02-01 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: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::Although the existence of t-tubules in mammalian cardiac ventricular myocytes has been recognized for a long time, it now appears that their structure and function are more complex than previously believed. Recent work has provided evidence that many of the key proteins underlying excitation-contraction coupling are l...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvm002
更新日期:2008-01-15 00:00:00
abstract:AIMS:Cardiac β-adrenergic receptors (β-AR) are key regulators of cardiac haemodynamics and size. The scaffolding protein A-kinase anchoring protein 79/150 (AKAP5) is a key regulator of myocardial signalling by β-ARs. We examined the function of AKAP5 in regulating cardiac haemodynamics and size, and the role of β-ARs a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu209
更新日期:2014-11-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine whether depressed myocardial contractility is responsible for the decline in stroke volume that occurs with cardiac tamponade. DESIGN:Left ventricular contractile performance was assessed before and after beta adrenergic blockade using the end systolic pressure-volume relation,...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.8.633
更新日期:1990-08-01 00:00:00
abstract::Segments of the canine ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta were instrumented with ultrasonic dimension gauges and a cathetertip manometer simultaneously to measure changes in segment diameter, length, and intravascular pressure. Volume distensibility (EV) was calculat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.6.385
更新日期:1988-06-01 00:00:00
abstract:OBJECTIVE:Hemodynamic stresses are considered to be important regulators of gene expression in vascular cells. In this study, we have investigated the role of shear stress on ACE expression in cultured rat vascular cells, and focused on the regulation of ACE expression in smooth muscle cells. METHODS:Rat aortic endoth...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00269-2
更新日期:2000-01-14 00:00:00
abstract::The role of the mitochondrial ATP-sensitive potassium channel (mK(ATP)) in ischemic preconditioning and cardioprotection is reviewed. A great deal of accumulated evidence implicatese opening of this channel as an important step in the anti-infarct effect of ischemic preconditioning. Recent studies, however, reveal tha...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(02)00439-x
更新日期:2002-08-15 00:00:00
abstract:AIMS:It is well established that dysfunction of voltage-dependent ion channels results in arrhythmias and conduction disturbances in the foetal and adult heart. However, the involvement of voltage-insensitive cationic TRPC (transient receptor potential canonical) channels remains unclear. We assessed the hypothesis tha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr167
更新日期:2011-11-01 00:00:00
abstract:STUDY OBJECTIVE:The aim was to determine whether taurine influences the membrane surface charges in cardiac muscle. DESIGN:Screening of the negative charges at the outside surface of the membrane results in a shift of the steady state inactivation of the sodium system towards less negative potentials. This feature was...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/24.11.918
更新日期:1990-11-01 00:00:00
abstract:OBJECTIVE:Cardiac energetics and performance depend on the expression level of the fast (alpha-) and slow (beta-) myosin heavy chain (MHC) isoform. In ventricular tissue, the beta-MHC isoform predominates, whereas in atrial tissue a variable mixture of alpha- and beta-MHC is found. In several cardiac diseases, the slow...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.09.029
更新日期:2005-01-01 00:00:00