Abstract：
:Mechanical stress signals transmitted through the heart walls during hemodynamic loading are sensed by the myocytes, which respond with changes in contractile performance and gene expression. External forces play an important role in physiological heart development and hypertrophy, but disruption of the well-balanced stress-sensing machinery causes mechanical dysregulation, cardiac remodelling, and heart failure. Nodal points of mechanosensing in the cardiomyocytes may reside in the Z-disk, I-band, and M-band regions of the sarcomeres. Longitudinal linkage of these regions is provided by the titin filament, and several 'hot spots' along this giant protein, in complex with some of its >20 ligands, may be pivotal to the myofibrillar stress or stretch response. This review outlines the known interaction partners of titin, highlights the putative stress/stretch-sensor complexes at titin's NH(2) and COOH termini and their role in myopathies, and summarizes the known disease-associated mutations in those titin regions. Another focus is the elastic I-band titin section, which interacts with a diverse number of proteins and whose main function is as a determinant of diastolic distensibility and passive stiffness. The discussion centers on recent insights into the plasticity, mechanical role, and regulation of the elastic titin springs during cardiac development and in human heart disease. Titin and titin-based protein complexes are now recognized as integral parts of the mechanosensitive protein network and as critical components in cardiomyocyte stress/stretch signalling.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Linke WAdoi
10.1016/j.cardiores.2007.03.029subject
Has Abstractpub_date
2008-03-01 00:00:00pages
637-48issue
4eissn
0008-6363issn
1755-3245pii
77/4/637journal_volume
77pub_type
杂志文章,评审abstract：OBJECTIVE:Growth hormone (GH) is known to induce growth of the normal rat heart. Whether this growth is due solely to hypertrophy of the cardiac myocytes or whether a concomitant hyperplasia of the cardiac myocytes also takes place is currently not known. Therefore, the aim of the present study was to investigate wheth...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2007.06.026
更新日期：2007-12-01 00:00:00
abstract：OBJECTIVE:Co-expression of the KvLQT1 and minK potassium channel subunits is required to recapitulate I(Ks), the slow component of the cardiac delayed rectifier current, and mutations in either gene cause the congenital Long QT syndrome. It is becoming increasingly well-recognized that multiprotein channel complexes co...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00498-4
更新日期：2002-10-01 00:00:00
abstract：AIMS:Doxorubicin (DOX) is widely used in cytostatic treatments, although it may cause cardiovascular dysfunction as a side effect. DOX treatment leads to enhanced free radical production that in turn causes DNA strand breakage culminating in poly(ADP-ribose) polymerase (PARP) activation and mitochondrial and cellular d...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr246
更新日期：2011-12-01 00:00:00
abstract：OBJECTIVE:The aim was to determine if either heparin or N-acetylheparin could reduce the extent of myocardial injury resulting from 90 min of coronary artery occlusion and 6 h of reperfusion in the anaesthetised dog. METHODS:Heparin or N-acetylheparin was given in three repeated intravenous doses of 2 mg.kg-1. Drug or...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：
更新日期：1995-05-01 00:00:00
abstract：:Blood vessels are permanently exposed to stretch and shear stress due to blood pressure and blood flow. Significant variations in the mechanical environment, of physiological or pathophysiological nature, occur in vivo. These trigger acute changes in vessel diameter that tend to restore basal levels of tensile and she...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/j.cardiores.2006.05.008
更新日期：2006-07-15 00:00:00
abstract：AIMS:Adverse cardiovascular events in humans occur with a day/night pattern, presumably related to a daily pattern of behaviours or endogenous circadian rhythms in cardiovascular variables. Healthy humans possess a scale-invariant/fractal structure in heartbeat fluctuations that exhibits an endogenous circadian rhythm ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvn150
更新日期：2008-10-01 00:00:00
abstract：OBJECTIVE:To investigate the physiological role of cAMP-dependent protein kinase A (PKA)-mediated, cardiac myosin binding protein C (MyBP-C) phosphorylation. METHODS:A cardiac MyBP-C cDNA lacking nine amino acids, which contained a phosphorylation site, was made, and subsequently used to generate multiple lines of tra...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00273-5
更新日期：2001-07-01 00:00:00
abstract：:There is evidence that catecholamines may promote the development of cardiac hypertrophy in hypertension. To test the hypothesis that adrenaline directly determines left ventricular mass, normotensive Wistar rats were made adrenaline-deficient by adrenalectomy and hypertensive by administration of glucocorticoid. Bloo...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/19.12.734
更新日期：1985-12-01 00:00:00
abstract：OBJECTIVE:Our aim was to determine in desmin homozygous mutant mice the viscoelastic properties, the mechanical strength and the structure of the carotid artery. METHODS:To assess the viscoelastic properties of large arteries, we have performed an in vivo analysis of the diameter-, and distensibility-pressure curves o...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(01)00278-4
更新日期：2001-07-01 00:00:00
abstract：:Cardiovascular diseases are among the main causes of morbidity and mortality in Western countries and considered as a leading public health issue. Therefore, there is a strong need for new disease models to support the development of novel therapeutics approaches. The successive improvement of genome editing tools wit...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvz250
更新日期：2020-04-01 00:00:00
abstract：AIMS:Peripheral chemoreflex sensitivity is potentiated in both clinical and experimental chronic heart failure (CHF). NADPH oxidase-derived superoxide mediates angiotensin II (Ang II)-enhanced carotid body (CB) chemoreceptor sensitivity in CHF rabbits, and tempol, the superoxide dismutase (SOD) mimetic, inhibits this A...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvn350
更新日期：2009-03-01 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：STUDY OBJECTIVE:The aim was to quantify the changes in placental blood flow and combined ventricular output with gestational age in normal human fetuses to determine the percentage of total cardiac output that placental blood flow represented, and whether this changed with age. DESIGN:Two dimensional echocardiographic...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/25.7.603
更新日期：1991-07-01 00:00:00
abstract：AIMS:TRPM2 is a Ca(2+)-permeable cationic channel of the transient receptor potential (TRP) superfamily that is linked to apoptotic signalling. Its involvement in cardiac pathophysiology is unknown. The aim of this study was to determine whether the pro-apoptotic cytokine tumour necrosis factor-α (TNF-α) induces a TRPM...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvu112
更新日期：2014-07-01 00:00:00
abstract：:To improve assessment of ventricular function during cardiac catheterisation there should be available a continuous registration of stroke volume and cardiac output in addition to ventricular pressure. To obtain the desired volumetric quantities a catheter has been developed which measures changes in intraventricular ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/15.6.328
更新日期：1981-06-01 00:00:00
abstract：OBJECTIVE:Effective endogenous fibrinolysis requires rapid release of endothelial tissue plasminogen activator (t-PA). Using the nitric oxide synthase inhibitor, L-NG-monomethylarginine (L-NMMA), we examined the contribution of endogenous nitric oxide to substance P-induced t-PA release in vivo in man. METHODS:Blood f...
journal_title：Cardiovascular research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1016/s0008-6363(98)00017-0
更新日期：1998-05-01 00:00:00
abstract：:There is mounting interest in the use of the monophasic action potential for electrophysiological investigation of regional myocardial ischaemia. There is, however, no systematic study of the relation between the changes in monophasic action potential and regional myocardial blood flow. In this study monophasic action...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/20.10.740
更新日期：1986-10-01 00:00:00
abstract：OBJECTIVE:Vascular smooth muscle cell (VSMC) de-differentiation is a prerequisite for migration from the tunica media to the intima after vascular injury. Integrin cell adhesion molecules participate in VSMC phenotype modulation. Alpha 8 beta 1 integrin is a differentiation marker of VSMCs and its knockdown heightens m...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2006.03.003
更新日期：2006-07-01 00:00:00
abstract：OBJECTIVE:We have attempted to demonstrate the induction of inducible nitric oxide synthase in human vascular tissue and define the capacity of different cytokines to induce this enzyme. METHODS:Segments of human arteries were stimulated with lipopolysaccharide (10 micrograms/ml), interleukin-1 beta (5 U/ml), tumor ne...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(98)00054-6
更新日期：1998-06-01 00:00:00
abstract：OBJECTIVE:Stem cells have significant potential for development of cell-based therapeutics for cardiovascular tissue regeneration. METHODS:We developed a novel method for isolating smooth muscle cells (SMC) from ovine bone marrow using a tissue-specific promoter and fluorescence-activated cell sorting. RESULTS:As com...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/j.cardiores.2007.04.018
更新日期：2007-08-01 00:00:00
abstract：OBJECTIVE:After-depolarization associated arrhythmias are frequently observed in heart failure and associated with spontaneous calcium release from sarcoplasmic reticulum (SR), calcium after-transients. We hypothesize that disturbed SR calcium handling underlies calcium after-transients in heart failure (HF). METHODS:...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1016/s0008-6363(02)00854-4
更新日期：2003-04-01 00:00:00
abstract：AIMS:Cholesteryl ester transfer protein (CETP) has a well-established role in lipoprotein metabolism, but the effect of its overexpression or inhibition on the efficiency of reverse cholesterol transport (RCT) is unclear. METHODS AND RESULTS:Neither overexpression of CETP nor treatment with CETP inhibitor Torcetrapib ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvm087
更新日期：2008-03-01 00:00:00
abstract：:Hyperhomocysteinemia is an independent risk factor for cardiovascular disease. Most previous investigations focused on the role of homocysteine as direct pathogenetic factor for these adverse vascular events. However, the exact pathophysiological mechanism is still unknown. In this review we discuss the hypothesis tha...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1016/s0008-6363(03)00462-0
更新日期：2003-08-01 00:00:00
abstract：:Excessive feeding is associated with an increase in the incidence of chronic metabolic diseases, such as obesity, insulin resistance, and type 2 diabetes. Metabolic disturbance induces chronic low-grade inflammation in metabolically-important organs, such as the liver and adipose tissue. Many of the inflammatory signa...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：10.1093/cvr/cvx012
更新日期：2017-03-15 00:00:00
abstract：OBJECTIVE:The aim was to investigate whether intrinsic cardiac neurones can be involved in the genesis of ventricular arrhythmias. METHODS:Nicotinic, muscarinic, beta adrenergic, peptidergic, and amino acidergic agonists, as well as purinergic compounds, were individually administered in microliter quantities adjacent...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/28.5.636
更新日期：1994-05-01 00:00:00
abstract：:Eicosanoids are important mediators of both physiological and pathophysiological responses of the microcirculation. These biologically active lipid mediators can be produced locally by the cellular elements within the microvasculature (endothelium, pericytes, smooth muscle cells) as well as interstitial cells (e.g. fi...
journal_title：Cardiovascular research
pub_type： 杂志文章,评审
doi：
更新日期：1996-10-01 00:00:00
abstract：AIMS:Previous studies on the role of stem cell factor (SCF) in endothelial progenitor cell (EPC)-mediated neovascularization have focused on the EPC mobilization and homing process. However, the direct effects of SCF on neovascularization activity of EPCs have not been characterized. We sought to determine whether SCF ...
journal_title：Cardiovascular research
pub_type： 杂志文章
doi：10.1093/cvr/cvr161
更新日期：2011-10-01 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：:This paper puts emphasis on pioneers who developed cardiac flow dynamics concepts during the second half of the 20th century at a period where pressure measurements were the rule. Thinking flow instead of pressure dynamics corresponded to in-depth conceptual changes: whereas blood pressure generally has a single posit...
journal_title：Cardiovascular research
pub_type： 社论,历史文章
doi：10.1016/s0008-6363(01)00307-8
更新日期：2001-08-01 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
