Abstract:
:Our own previous ultrastructural studies in human hearts with dilated cardiomyopathy and heart failure showed sarcomeric and cytoskeletal disarrangement. On the basis of these findings we tested the hypothesis that in cardiomyopathic failing hearts not only the sarcomere structure but also the organization and the amount of numerous contractile proteins are disturbed. Titin was included in this study because it is the elastic "third" filament of the sarcomere and also plays an important role as template for myosin and actin filaments in sarcomerogenesis. Human cardiac tissue obtained at the time of transplantation surgery was investigated using immunohistochemistry with monoclonal antibodies against titin, myosin, actin, tropomyosin, and troponin T. Additionally, isolated myocytes from rat or pig heart were used for the standardization of the localization pattern. In normal tissue, myosin and the thin filament complex showed a regular cross striation that was wider in myosin staining than for actin, troponin T, and tropomyosin corresponding with the different width of the A and I bands in the sarcomere. Titin localization in normal human and animal myocardium showed a regular cross striation pattern. In diseased cardiac tissue titin fluorescence intensity was reduced and frequently disorganization or almost complete loss of titin from many myocytes were present. Severe abnormalities of contractile proteins consisting of disarrangement or lack of filaments were also observed. Double staining procedures showed that in the same myocyte defects of the contractile apparatus were accompanied by a simultaneous reduction of titin indicating that the "third" sarcomeric filament system is involved in heart failure. Abnormalities of titin expression may be especially important because titin significantly influences sarcomeric elastic behaviour and is necessary as template for the organization of newly synthesized myosin and actin filaments. The loss of titin may contribute to the altered compliance in failing hearts. It is concluded that disorganization and loss of titin, myosin, and the thin filament complex are severe in the failing human heart because of dilated cardiomyopathy and that these changes may represent several of the most important components of the structural correlate of reduced cardiac function.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Hein S,Scholz D,Fujitani N,Rennollet H,Brand T,Friedl A,Schaper Jdoi
10.1006/jmcc.1994.1148subject
Has Abstractpub_date
1994-10-01 00:00:00pages
1291-306issue
10eissn
0022-2828issn
1095-8584pii
S0022-2828(84)71148-5journal_volume
26pub_type
杂志文章abstract::This study addressed the question whether the molecular mass of proteins influences their release from isolated rat neonatal cardiomyocytes subjected to simulated ischemia (SI) or metabolic inhibition (MI). During these interventions cellular ATP content and the relative releases of several proteins, ranging in molecu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0133
更新日期:1996-07-01 00:00:00
abstract::The transformation of vascular smooth muscle cells [VSMC] into foam cells leading to increased plaque size and decreased stability is a key, yet understudied step in atherogenesis. We reported that Interleukin-19 (IL-19), a novel, anti-inflammatory cytokine, attenuates atherosclerosis by anti-inflammatory effects on V...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.02.005
更新日期:2017-04-01 00:00:00
abstract::Familial hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy with an autosomal dominant pattern of inheritance. The disease bearing genes for HCM in HCM families have been identified as beta-myosin heavy chain, alpha-tropomyosin, cardiac troponin T (cTnT) and myosin binding protein-C genes. In the present st...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0322
更新日期:1997-02-01 00:00:00
abstract::The cardiac muscle sarcomere contains multiple proteins contributing to contraction energy transduction and its regulation during a heartbeat. Inheritable heart disease mutants affect most of them but none more frequently than the ventricular myosin motor and cardiac myosin binding protein c (mybpc3). These co-localiz...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2018.04.006
更新日期:2018-06-01 00:00:00
abstract::We have previously proposed that the heterogeneous collapse of mitochondrial inner membrane potential (DeltaPsi(m)) during ischemia and reperfusion contributes to arrhythmogenesis through the formation of metabolic sinks in the myocardium, wherein clusters of myocytes with uncoupled mitochondria and high K(ATP) curren...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.11.011
更新日期:2010-04-01 00:00:00
abstract::Myocardial infarction (MI) is one of the leading causes of morbidity and mortality world-wide. Whether endogenous repair and regenerative ability could be augmented by drug administration is an important issue for generation of novel therapeutic approach. Recently it was reported that in mice pretreated with thymosin ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.08.020
更新日期:2012-01-01 00:00:00
abstract:RATIONALE:How ischemic postconditioning can inhibit opening of the mitochondrial permeability transition pore (PTP) and subsequent cardiac myocytes death at reperfusion remains unknown. Recent studies have suggested that de-acetylation of cyclophilin D (CyPD) by sirtuin 3 (SIRT3) can modulate its binding to the PTP. O...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.03.017
更新日期:2015-07-01 00:00:00
abstract::The failure of adenosine receptor antagonists to consistently attenuate metabolic coronary vasodilation suggests that adenosine is not a primary regulator of functional hyperemia. An alternative hypothesis, however, is that metabolic stimulation of the heart in the presence of an adenosine receptor antagonist results ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(91)90132-6
更新日期:1991-08-01 00:00:00
abstract::The key information processing units within gene regulatory networks are enhancers. Enhancer activity is associated with the production of tissue-specific noncoding RNAs, yet the existence of such transcripts during cardiac development has not been established. Using an integrated genomic approach, we demonstrate that...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.08.009
更新日期:2014-11-01 00:00:00
abstract::Ca(2+) flux through l-type CaV1.2 channels shapes the waveform of the ventricular action potential (AP) and is essential for excitation-contraction (EC) coupling. Timothy syndrome (TS) is a disease caused by a gain-of-function mutation in the CaV1.2 channel (CaV1.2-TS) that decreases inactivation of the channel, which...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2013.10.021
更新日期:2014-01-01 00:00:00
abstract::The purpose of this study was to investigate whether vitamin D3 deficiency affects the cardiac function of chick hearts directly or whether the influence is secondary through the hormone's effect on serum calcium levels. To this end, three experimental groups were studied: (a) the control group of vitamin D3 supplemen...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1993.1010
更新日期:1993-01-01 00:00:00
abstract::Vascular cells are very sensitive to their hemodynamic environment. Any change in blood pressure or blood flow can be sensed by endothelial and vascular smooth muscle cells and ultimately results in structural modifications within the vascular wall that accommodate the new conditions. In the case of hypertension, the ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2009.09.018
更新日期:2010-03-01 00:00:00
abstract::Perlecan, a basal lamina proteoglycan, has been shown to interact with other extracellular matrix (ECM) components, especially type IV collagen, and is thus involved in ECM formation. Perlecan has also been postulated to promote growth factor-receptor interactions, including the binding of basic fibroblast growth fact...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2000.1146
更新日期:2000-06-01 00:00:00
abstract::Free radical generating systems produce a sequence of changes in the action potentials of isolated cardiac myocytes. Efforts to understand the nature of the alterations in ionic currents have yielded mixed results. The use of patch-pipettes for voltage-clamp experiments and manipulation of pipette solution composition...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1068
更新日期:1994-05-01 00:00:00
abstract::Increasing evidence suggests that derangements of cytoskeletal proteins contribute to alterations in intracellular signaling, myocyte function, and the coupling of myocytes to the extracellular matrix during cardiac hypertrophy and failure. Data from animal studies have shown an increased density of beta-tubulin prote...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2002.2105
更新日期:2002-11-01 00:00:00
abstract::Viscosity is proposed to modulate diastolic function, but only limited understanding of the source(s) of viscosity exists. In vitro experiments have shown that the proline-glutamic acid-valine-lysine (PEVK) rich element of titin interacts with actin, causing a viscous force in the sarcomere. It is unknown whether this...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2011.06.006
更新日期:2011-09-01 00:00:00
abstract::Titin is a very large alternatively spliced protein that performs multiple functions in heart and skeletal muscles. A rat strain is described with an autosomal dominant mutation that alters the isoform expression of titin. While wild type animals go through a developmental program where the 3.0 MDa N2B becomes the maj...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.02.272
更新日期:2008-06-01 00:00:00
abstract::In recently published studies, we show that angiotensin II (AII) generated from an engineered rat angiotensinogen cDNA, and maintained intracellularly, is growth stimulatory for a rat hepatoma cell line. In the present study, we report that co-expression of AII fused to cyan fluorescent protein (ECFP/AII) and angioten...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2003.09.021
更新日期:2004-01-01 00:00:00
abstract::Cardiac hypertrophy is associated with modifications in Ca2+ transport processes, enzymes of energy metabolism and antioxidant capacity. It is unknown whether these changes occur in infarct-induced hypertrophy with regard to an altered susceptibility to ischemia/reperfusion injury. We examined changes in sarcoplasmic ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0794
更新日期:1998-11-01 00:00:00
abstract::The specific activity of cardiac cathepsin B is significantly decreased by starvation and corticosteroid treatment in vivo, and by exposure of the heart in vitro to insulin, hydrocortisone and cycloheximide. Increases in cathepsin B activity occur following isoproterenol-induced cardiac damage in vivo and exposure in ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(83)90324-3
更新日期:1983-08-01 00:00:00
abstract::The self-perpetuation of atrial fibrillation (AF) is associated with atrial remodeling, including the degradation of the myofibril structure (myolysis). Myolysis is related to AF-induced activation of cysteine proteases and underlies loss of contractile function. In this study, we investigated which proteases are invo...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.08.012
更新日期:2008-11-01 00:00:00
abstract::Lack of endothelial nitric oxide synthase (eNOS) may affect the sensitivity of cyclic GMP signaling through soluble guanylyl cyclase (sGC). We hypothesized that in eNOS knockout (eNOS-/-) mice, stimulation of guanylyl cyclase would have enhanced effects inhibiting cardiac contraction. We measured cell shortening and c...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2005.08.008
更新日期:2005-12-01 00:00:00
abstract::The effects of fentanyl on ultrastructure, protein biosynthesis, and atrial natriuretic peptide (ANP) secretion were studied in neonatal rat cardiomyocytes (CM). Ventricles from 2-day-old American Wistar rats were digested with 1% collagenase in perfusion buffer. Eight hundred thousand to 1.0 million cells/ml were inc...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1053
更新日期:1994-04-01 00:00:00
abstract::The interaction of verapamil and other phenylalkylamine calcium channel blockers with the 1,4-dihydropyridine receptor was examined. Studies characterizing the interaction and relationship between calcium channel blocking potency and binding affinity were performed in rat myocardium. The 1,4-dihydropyridines, nifedipi...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80010-4
更新日期:1986-09-01 00:00:00
abstract::During systole, Ca2+ is released from the sarcoplasmic reticulum (SR) through ryanodine receptors (RyRs) while, simultaneously, other ions (specifically K+, Mg2+, and Cl-) provide counter-ion flux. These ions move back into the SR during diastole through the SERCA pump and SR K+ and Cl- channels. In homeostasis, all i...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2016.10.018
更新日期:2017-02-01 00:00:00
abstract::Almost 7 years have passed since the initial publication reporting that bone marrow cells regenerate infarcted myocardium. The subsequent years produced hundreds of investigations that ran the gamut of findings from validation to disproof. Undeterred by the concurrent debate, clinical trials ensued to test the safety ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2008.03.007
更新日期:2008-06-01 00:00:00
abstract::Microtubules have been implicated in a number of muscle-specific functions, including sarcomerogenesis and the regulation of heart cell beating rate. Post-translationally modified microtubules (MTs) have been correlated, in other cell types, with MTs of increased stability and possibly distinct functions. This study w...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0421
更新日期:1997-06-01 00:00:00
abstract::In susceptible DBA/2 mice coxsackievirus B 3-induced myocarditis leads to inflammatory and necrotic lesions in the myocardium 7-10 days after virus inoculation. The purpose of this study was to determine whether hemodynamic changes occur in murine coxsackievirus B 3 myocarditis and whether they are correlated to histo...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(95)90425-5
更新日期:1995-08-01 00:00:00
abstract::The incidence of ventricular arrhythmias is higher in failing hearts than in control hearts, especially during acute ischemia. Electrophysiological and extracellular ionic changes during acute ischemia in normal and failing rabbit myocardium were assessed. Heart failure was induced in rabbits by combined volume and pr...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0012
更新日期:1996-01-01 00:00:00
abstract::Ischemia-induced myocardial potassium loss and post-ischemic potassium reuptake was quantitated in 8 open chest pigs during control conditions and during hemodynamic alterations which have been shown to increase steady state sarcolemmal potassium fluxes. Myocardial K+ balance was continuously computed before, during a...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(89)90673-1
更新日期:1989-12-01 00:00:00