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 hypothesized that HO-1 and its catalytic by-products constitute an antihypertrophic signaling module in cardiac myocytes. METHODS AND RESULTS:The G protein-coupled receptor (GPCR) agonist endothelin-1 (ET-1) (30 nmol/l) stimulated a robust hypertrophic response in cardiac myocytes isolated from 1- to 3-day-old Sprague-Dawley rats, with increases in cell surface area (planimetry), sarcomere assembly (confocal laser scanning microscopy), and prepro-atrial natriuretic peptide (ANP) mRNA expression. Adenoviral overexpression of HO-1, but not beta-galactosidase, significantly inhibited ET-1 induced cardiac myocyte hypertrophy. The antihypertrophic effects of HO-1 were mimicked by BV (10 micromol/l) and the CO-releasing molecule [Ru(CO)3Cl2]2 (10 micromol/l), strongly suggesting a critical involvement of BV and CO in the antihypertrophic effects of HO-1. Both BV and CO suppressed extracellular signal-regulated kinases (ERK1/ERK2) and p38 mitogen-activated protein kinase (MAPK) activation by ET-1 stimulation. Moreover, BV and CO inhibited the prohypertrophic calcineurin/NFAT pathway. This inhibition occurred upstream from calcineurin because BV and CO inhibited NFAT activation in response to ET-1 stimulation but not in response to adenoviral expression of a constitutively active calcineurin mutant. Upstream-inhibition of the calcineurin/NFAT pathway by CO occurred independent from cGMP and cGMP-dependent protein kinase type I (PKG I). CONCLUSIONS:Heme oxygenase-1 and its catalytic by-products, BV and CO, constitute a novel antihypertrophic signaling pathway in cardiac myocytes. Biliverdin and CO inhibition of MAPKs and calcineurin/NFAT signaling provides a mechanistic framework how heme degradation products may promote their antihypertrophic effects.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Tongers J,Fiedler B,König D,Kempf T,Klein G,Heineke J,Kraft T,Gambaryan S,Lohmann SM,Drexler H,Wollert KCdoi
10.1016/j.cardiores.2004.04.015subject
Has Abstractpub_date
2004-08-15 00:00:00pages
545-52issue
3eissn
0008-6363issn
1755-3245pii
S0008636304001750journal_volume
63pub_type
杂志文章abstract::Elevated sympathetic activity changes renal function and accelerates the development of hypertension. Principles of sympatho-renal interactions in chronic hypertension are reviewed. Alterations in the ontogeny of the sympathetic nervous system and the kidney, inherited abnormalities in sensory receptor function and ex...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2003.11.024
更新日期:2004-02-01 00:00:00
abstract:OBJECTIVE:Ischemic postconditioning protects the reperfused heart from infarction, and this protection is dependent on the occupancy of adenosine receptors. We further explored the role of adenosine receptors in this salvage. METHODS:In situ rabbit hearts underwent 30 min of regional ischemia and 3 h of reperfusion, a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2006.02.014
更新日期:2006-05-01 00:00:00
abstract:OBJECTIVE:Air bubbles entering the coronary artery may have harmful effects on cardiac function. From the physical point of view it is the relatively high surface tension of the blood-air interface which causes bubbles to trap in small vessels. The aim of the present study was to reduce depression of myocardial functio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(97)00063-1
更新日期:1997-06-01 00:00:00
abstract::Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissectio...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvy006
更新日期:2018-03-15 00:00:00
abstract:OBJECTIVE:A circadian rhythm of blood pressure has been demonstrated both in subjects who are physically active during the day and in those confined to bed. The study of the circadian rhythm of arterial flow and peripheral resistance, on the other hand, is limited to pioneer experiments. This paper is aimed at demonstr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00237-5
更新日期:1999-01-01 00:00:00
abstract::The heart is challenged by a plethora of extracellular stimuli over the course of a normal day, each of which distinctly influences myocardial contractile function. It is therefore not surprising that myocardial metabolism also oscillates in a time-of-day dependent manner. What is becoming increasingly apparent is tha...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvn054
更新日期:2008-07-15 00:00:00
abstract:AIMS:Heart failure is associated with deficient endothelial nitric oxide (NO) production as well as increased oxidative stress and accelerated NO degradation. The aim of this study was to evaluate platelet NO biosynthesis and superoxide anion (O(2)(-)) production in patients with heart failure. METHODS AND RESULTS:In ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr115
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:The functional status of heart failure (HF) is conventionally evaluated by peak exercise oxygen consumption (VO2 max). Dobutamine echocardiography can be used to evaluate myocardial reserve. The aim of this study was to estimate the functional status of chronic HF in patients with dilated cardiomyopathy, by ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00345-9
更新日期:1999-07-01 00:00:00
abstract:AIMS:Antihypertensive drugs are included in the medical therapy of vascular Ehlers-Danlos syndrome (vEDS). The β-blocker celiprolol has been suggested to prevent arterial damage in vEDS, but the underlying mechanism remains unclear. It is also unknown whether the widely used angiotensin II receptor type 1 antagonist lo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz095
更新日期:2020-02-01 00:00:00
abstract:OBJECTIVE:The aim was to study the contractility of the conduit coronary artery to vasoactive agents in developing and established volume overload cardiac hypertrophy and to compare it with structural alterations in the artery. METHODS:Aortic valve insufficiency in rabbits was used to produce a volume overloaded heart...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.11.2005
更新日期:1993-11-01 00:00:00
abstract:AIMS :Activation of the angiotensin (Ang)-(1-7)/Mas receptor (R) axis protects from sympathetic overactivity. Endocytic trafficking is an essential process that regulates receptor (R) function and its ultimate cellular responses. We investigated whether the blunted responses to Ang-(1-7) in hypertensive rats are associ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz332
更新日期:2020-10-01 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:OBJECTIVES:Coronary artery often reoccludes after thrombolytic therapy with recombinant tissue-plasminogen activator (rt-PA). This reocclusion is thought to be due to in situ platelet activation mediated by thromboxane (Tx) A2 and thrombin; hence, aspirin and thrombin inhibitors are often used in patients with acute my...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-12-01 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::The effect of lidocaine on the effective refractory period of the right ventricle (EVRP) was measured in 10 patients using the extra stimulus technique of progressive introduction of premature stimuli until a response could not be elicited. In four patients lidocaine produced a significant decrease in the EVRP, in a f...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/9.5.621
更新日期:1975-09-01 00:00:00
abstract::The effects of repeated (10 X), brief Ca2+-free perfusions (20 to 120 s) on myocardial contractility, coronary flow and release of cellular constituents of isolated rat heart were investigated. Ten successive Ca2+-deprivations of 20 or 40 s had no irreversible influences on cardiac performance. Ca2+-deprivations, howe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/17.8.476
更新日期:1983-08-01 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:AIMS:Our aim was to determine whether the repeated, binge administration of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) produces structural and/or functional changes in the myocardium that are associated with oxidative stress. METHODS AND RESULTS:Echocardiography and pressure-volume conductance catheters were us...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn129
更新日期:2008-09-01 00:00:00
abstract::If the posterior hypothalamus contributes to elevate blood pressure in hypertension by increasing sympathetic vasomotor activity, then lesions of the posterior hypothalamus should lower blood pressure more in hypertensive than in normotensive rats. To test this hypothesis without complications caused by anaesthesia, a...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/10.6.663
更新日期:1976-11-01 00:00:00
abstract:AIMS:The human ether-a-go-go-related gene (hERG) encodes the rapidly activating delayed rectifier potassium channel (IKr). Malfunction of hERG/IKr is the primary cause of acquired long QT syndrome (LQTS), an electrical disorder of the heart that can cause arrhythmias and sudden death. Patients with autoimmune diseases ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy310
更新日期:2019-08-01 00:00:00
abstract::Congenital coronary artery anomalies are of major significance in clinical cardiology and cardiac surgery due to their association with myocardial ischaemia and sudden death. Such anomalies are detectable by imaging modalities and, according to various definitions, their prevalence ranges from 0.21 to 5.79%. This cons...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv251
更新日期:2016-02-01 00:00:00
abstract::We studied the effects of intravenously administered autonomic agents, the calcium channel blocker diltiazem, and Class I and III anti-arrhythmic agents on a re-entry model for atrial tachycardia in seven conscious dogs. The model was created by a Y-shaped incision in the intercaval region and front free wall of the r...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.5.400
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:AIMS:In cardiomyocytes, protein kinase D1 (PKD1) plays a central role in the response to stress signals. From a yeast two-hybrid assay, we have identified Enigma Homolog 1 (ENH1) as a new binding partner of PKD1. Since in neurons, ENH1, associated with protein kinase Cepsilon, was shown to modulate the activity of N-ty...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn052
更新日期:2008-06-01 00:00:00
abstract:AIMS:Pulmonary hypertension (PH) is a devastating condition for which no disease-modifying therapies exist. PH is recognized as proliferative disease of the pulmonary artery (PA). In the experimental newborn calf model of hypoxia-induced PH, adventitial fibroblasts in the PA wall exhibit a heightened replication index....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs194
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVE:Persistent supraventricular tachycardia leads to the development of a dilated cardiomyopathy with impairment of excitation-contraction (EC) coupling. Since the initial trigger for EC coupling in ventricular muscle is the influx of Ca(2+) through L-type Ca(2+) channels (I(Ca)) in the transverse tubules (T-tubu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(00)00256-x
更新日期:2001-02-01 00:00:00
abstract::Atrial fibrillation (AF) is a very common clinical problem, and presently available treatment options are suboptimal. A tremendous amount has been learned over the past 10 years about the atrial substrates that support sustained AF at the tissue, ionic and molecular levels. This understanding of the fundamental mechan...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(01)00562-4
更新日期:2002-05-01 00:00:00
abstract:AIMS:The mesenchymal cushions lining the early embryonic heart undergo complex remodelling to form the membranous ventricular septum as well as the atrioventricular and semilunar valves in later life. Disruption of this process underlies the most common congenital heart defects. Here, we identified a novel role for Sli...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvv040
更新日期:2015-04-01 00:00:00
abstract::Cardiomyocytes are long-lived post-mitotic cells with limited regenerative capacity. Proper cardiomyocyte function depends critically on the maintenance of a healthy homeostasis of protein expression, folding, assembly, trafficking, function, and degradation, together commonly referred to as proteostasis. Impairment o...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv265
更新日期:2016-04-01 00:00:00
abstract:OBJECTIVE:The role of phosphorylation of the ryanodine receptor at serine-2808 (RyRS2808) in congestive heart failure (CHF) is controversial, and effects of RyRS2808 phosphorylation on contraction are unclear. It has been reported that diastolic sarcomere length (SL) fluctuations accompany propagating contractile waves...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.07.010
更新日期:2006-01-01 00:00:00