Abstract:
AIMS:The overloaded heart remodels by cardiomyocyte hypertrophy and interstitial fibrosis, which contributes to the development of heart failure. Signalling via the TGFβ-pathway is crucial for this remodelling. Here we tested the hypothesis that microRNAs in the overloaded heart regulate this remodelling process via inhibition of the TGFβ-pathway. METHODS AND RESULTS:We show that the miRNA-15 family, which we found to be up-regulated in the overloaded heart in multiple species, inhibits the TGFβ-pathway by targeting of TGFBR1 and several other genes within this pathway directly or indirectly, including p38, SMAD3, SMAD7, and endoglin. Inhibition of miR-15b by subcutaneous injections of LNA-based antimiRs in C57BL/6 mice subjected to transverse aorta constriction aggravated fibrosis and to a lesser extent also hypertrophy. CONCLUSION:We identified the miR-15 family as a novel regulator of cardiac hypertrophy and fibrosis acting by inhibition of the TGFβ-pathway.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Tijsen AJ,van der Made I,van den Hoogenhof MM,Wijnen WJ,van Deel ED,de Groot NE,Alekseev S,Fluiter K,Schroen B,Goumans MJ,van der Velden J,Duncker DJ,Pinto YM,Creemers EEdoi
10.1093/cvr/cvu184subject
Has Abstractpub_date
2014-10-01 00:00:00pages
61-71issue
1eissn
0008-6363issn
1755-3245pii
cvu184journal_volume
104pub_type
杂志文章abstract:AIMS:in this study, we attempted to detect a recent myocardial ischaemic event using ultrasound molecular imaging (UMI) with microbubbles (MB) targeted to intercellular adhesion molecule-1 (ICAM-1) in the late phase of reperfusion. METHODS AND RESULTS:we created a myocardial ischaemia-reperfusion model in 60 C57/BL ma...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq269
更新日期:2011-01-01 00:00:00
abstract:AIMS:17β-Oestradiol (E2) and its receptors (ERα and ERβ) are important regulators of physiological and pathological processes in the cardiovascular system. ER act in concert with other regulatory factors mediating oestrogenic effects. However, the underlying mechanisms modulating ER transcriptional activity are not ful...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs281
更新日期:2012-12-01 00:00:00
abstract:AIMS:Neovascularization is an important element of long-term functional recovery during chronic ischaemia. We postulated that haeme oxygenase (HO) is required for progenitor cell recruitment, neovascularization, and blood flow recovery after critical hindlimb ischaemia (HLI). METHODS AND RESULTS:The femoral artery was...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvm107
更新日期:2008-05-01 00:00:00
abstract:OBJECTIVE:The aim was to investigate the influence of coronary occlusion on myocardial interstitial noradrenaline levels in the ischaemic and non-ischaemic regions, using the dialysis technique. METHODS:In nine anaesthetised cats, regional ischaemia was produced by occlusion of the left anterior descending coronary ar...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.5.817
更新日期:1993-05-01 00:00:00
abstract:AIMS:To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes. METHODS AND RESULTS:Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa241
更新日期:2020-08-10 00:00:00
abstract::Following a myocardial infarction (MI), the immune system helps to repair ischaemic damage and restore tissue integrity, but excessive inflammation has been implicated in adverse cardiac remodelling and development towards heart failure (HF). Pre-clinical studies suggest that timely resolution of inflammation may help...
journal_title:Cardiovascular research
pub_type: 杂志文章,meta分析
doi:10.1093/cvr/cvy145
更新日期:2018-09-01 00:00:00
abstract:OBJECTIVE:Activation of peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma plays beneficial roles in cardiovascular disorders such as atherosclerosis and heart reperfusion. Although PPARalpha and gamma have been documented to reduce oxidative stress in the vasculature and the heart, the role of ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.10.019
更新日期:2006-02-01 00:00:00
abstract:AIMS:Hydrogen sulphide (H(2)S) is an endogenously generated gaseous transmitter that has recently been suggested to regulate cardiovascular functions. To date, there is no direct evidence for a potential role of H(2)S in regulating calcium channels in the heart. The present study aims to examine the hypothesis that H(2...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn140
更新日期:2008-09-01 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:OBJECTIVE:The aim was to investigate the effect of increased left ventricular filling pressure on the pulmonary vein flow (PVQ) pattern. METHODS:Pulmonary vein flow was recorded using an ultrasonic transit time flow meter in six anaesthetised dogs. Mean left atrial pressure was increased by stepwise volume loading fro...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.3.411
更新日期:1993-03-01 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::We have studied the responses to a brief interruption of a train of steady state beats, namely: (1) a single prolonged depolarisation within the train; (2) a single short interval within the train; (3) a single long interval within the train. These responses are predicted by a two compartment model of intracellular ca...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.10.1758
更新日期:1993-10-01 00:00:00
abstract:OBJECTIVE:The human ether-a-go-go-related gene (hERG) encodes the rapid component of the cardiac repolarizing delayed rectifier potassium current, I(Kr). The direct interaction of the commonly used protein kinase C (PKC) inhibitor bisindolylmaleimide I (BIM I) with hERG, KvLQT1/minK, and I(Kr) currents was investigated...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.07.023
更新日期:2004-12-01 00:00:00
abstract:OBJECTIVE:Both superoxide dismutase (SOD) and nitric oxide synthase (NOS) have been implicated in delayed preconditioning (DP) to ischemia/reperfusion (I/R) in the heart. We used isolated cardiac myocytes to test the hypothesis that SOD and NOS may interact in the development of DP. METHODS:Mouse neonatal cardiac myoc...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00502-9
更新日期:2003-10-01 00:00:00
abstract::Diabetes is one of the most prevalent chronic conditions that has a high association with death from cardiovascular disease(s). An impaired cardiac function independent of vascular disease suggests the existence of a primary myocardial defect in diabetes mellitus. We and others have documented that myocardial performa...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(97)00059-x
更新日期:1997-04-01 00:00:00
abstract::The development of the heart is a complex process during which different cell types progressively contribute to shape a four-chambered pumping organ. Over the last decades, our understanding of the specification and transcriptional regulation of cardiac development has been greatly augmented as has our understanding o...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvr078
更新日期:2011-07-15 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:Macrophage-related oxidative stress plays an important role in the inflammatory process in atherosclerosis. Recently, dextromethorphan (DXM), a common cough-suppressing ingredient with a high safety profile, was found to inhibit the activation of microglia, the resident macrophage in the nervous system. We investi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp043
更新日期:2009-04-01 00:00:00
abstract::Ultrasound has become a useful high resolution imaging modality for examining the cardiac microcirculation. With the use of microbubbles as an ultrasound contrast agent, ultrasound can be utilized to image the microcirculation and detect capillary flow abnormalities in acute ischaemia. A wide range of ultrasound frequ...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvp206
更新日期:2009-09-01 00:00:00
abstract::The heart contains not only cardiomyocytes but also other cell types such as endothelial cells and fibroblasts. Functional crosstalk among these cell types is important for normal cardiac function and is also involved in disease pathophysiology. Recent data indicate that redox signalling within and between endothelial...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvu050
更新日期:2014-05-01 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::Regional distribution of myocardial blood flow (MBF) was examined in eight normal and nine pulmonary artery banded (PAB) pigs before and during pacing induced tachycardia (heart rates: 175, 225 and 275 beats X min-1) as well as during iv adenosine infusion (1.5 mg X kg-1 X min-1; maximal coronary vasodilatation) using...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.2.104
更新日期:1985-02-01 00:00:00
abstract:OBJECTIVES:Epidemiological evidence in humans suggests that intrauterine growth retardation is associated with an increased risk of hypertension and coronary heart disease in later life. To begin to understand the mechanisms involved, we developed and exploited a rat model of intrauterine growth retardation to assess p...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00167-x
更新日期:2000-11-01 00:00:00
abstract:OBJECTIVE:Numerous studies support the concept of impaired postischemic sympathetic neurotransmission in the heart. We hypothesized that postischemic neuronal dysfunction (neuronal stunning) is caused by a transient suppression of exocytotic norepinephrine (NE) release from sympathetic nerve terminals. Furthermore, we ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00309-6
更新日期:2001-03-01 00:00:00
abstract::To examine how end systole differs from end ejection and also whether the slope of the end systolic pressure-volume relation can be approximated to that of the end ejection pressure-volume relation, nine isolated, perfused, paced canine hearts ejecting into a hydraulic loading system that simulated the aortic input im...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.2.107
更新日期:1987-02-01 00:00:00
abstract::Genetic and environmental factors influence the development of coronary artery disease (CAD). Genetic analyses of families and the population continue to yield important fundamental insights for CAD. For the past four decades, CAD human genetic research focused largely on the study of germline genetic variation in CAD...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvz032
更新日期:2019-04-15 00:00:00
abstract:OBJECTIVE:Heme oxygenases (HO) are the rate-limiting enzymes in heme degradation, catalyzing the breakdown of heme to equimolar quantities of biliverdin (BV), carbon monoxide (CO), and ferrous iron. The inducible HO isoform, HO-1, confers protection against ischemia/reperfusion (I/R)-injury in the heart. We hypothesize...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.04.015
更新日期:2004-08-15 00:00:00
abstract::We studied the effects of intracoronary vasopressin on the relationship between pressure and flow in the coronary circulation of anaesthetised swine. In addition to measurements at control levels, diastolic pressure-flow relationships were constructed from steady-state points below a coronary pressure of 50 mmHg, wher...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/19.7.433
更新日期:1985-07-01 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:OBJECTIVE:The objective of this study was to explore the relationship between low density lipoprotein (LDL) and dendritic cell (DC) activation, based upon the hypothesis that reactive oxygen species (ROS)-mediated modification of proteins that may be present in local DC microenvironments could be important as mediators...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00447-9
更新日期:2002-09-01 00:00:00