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 mechanism contributes to viscosity in vivo. We tested the hypothesis that PEVK-actin interaction causes cardiac viscosity and is important in vivo via an integrative physiological study on a unique PEVK knockout (KO) model. Both skinned cardiomyocytes and papillary muscle fibers were isolated from wildtype (WT) and PEVK KO mice and passive viscosity was examined using stretch-hold-release and sinusoidal analysis. Viscosity was reduced by ~60% in KO myocytes and ~50% in muscle fibers at room temperature. The PEVK-actin interaction was not modulated by temperature or diastolic calcium, but was increased by lattice compression. Stretch-hold and sinusoidal frequency protocols on intact isolated mouse hearts showed a smaller, 30-40% reduction in viscosity, possibly due to actomyosin interactions, and showed that microtubules did not contribute to viscosity. Transmitral Doppler echocardiography similarly revealed a 40% decrease in LV chamber viscosity in the PEVK KO in vivo. This integrative study is the first to quantify the influence of a specific molecular (PEVK-actin) viscosity in vivo and shows that PEVK-actin interactions are an important physiological source of viscosity.
journal_name
J Mol Cell Cardioljournal_title
Journal of molecular and cellular cardiologyauthors
Chung CS,Methawasin M,Nelson OL,Radke MH,Hidalgo CG,Gotthardt M,Granzier HLdoi
10.1016/j.yjmcc.2011.06.006subject
Has Abstractpub_date
2011-09-01 00:00:00pages
428-34issue
3eissn
0022-2828issn
1095-8584pii
S0022-2828(11)00226-4journal_volume
51pub_type
杂志文章abstract::Studies of hemodynamics and intrinsic left ventricular myocardial function are carried out to investigate the transition from stable hypertrophy to cardiac decompensation in the aging (18-24 months) spontaneously hypertensive rat (SHR). Echocardiographic data in awake animals demonstrate increased end-diastolic and en...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(08)80035-1
更新日期:1995-01-01 00:00:00
abstract::Increasing bodies of evidence indicate that reactive oxygen species (ROS) produced by mitochondria and other sources play an essential role in mediating ventricular remodeling after myocardial infarction and the development of heart failure. Antioxidants scavenge ROS, thereby maintaining the reduced environment of cel...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2006.08.006
更新日期:2006-11-01 00:00:00
abstract::The activation of NO/cGMP pathways can induce pro-apoptotic pathways in cardiomyocytes although only a small number of cardiomyocytes fulfill the criteria of apoptosis. The same pathways reduce the contractile performance of cardiomyocytes. In the present study, we tested the hypothesis that exposure of cells to NO/cG...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2006.10.012
更新日期:2007-02-01 00:00:00
abstract::The purposes of this study were to: (1) assess myocardial pyruvate dehydrogenase (PDH) activity and substrate exchange under well-perfused and ischemic conditions; (2) determine the metabolic effects of an intra-coronary infusion of the PDH activator, dichloroacetate (DCA); and (3) measure the effects of ischemia and ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0085
更新日期:1996-05-01 00:00:00
abstract::To investigate the interaction of cytoskeleton with the receptor modulation of ionic currents, we studied the effect of muscarinic and beta-adrenergic stimulation in adult guinea-pig ventricular cardiac myocytes treated with paclitaxel and colchicine, two drugs that respectively stabilize or destabilize microtubules. ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(02)00312-7
更新日期:2003-02-01 00:00:00
abstract::Function and various parameters of myocardial substrate and energy metabolism were measured in preload-controlled isolated working guinea-pig hearts perfused with normoxic (95% O2) and hypoxic (30 to 45% O2) Krebs-Henseleit buffers ([Ca2+] = 1.25 mM). Energy-yielding substrates were glucose, pyruvate, lactate, and fat...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(86)80905-1
更新日期:1986-04-01 00:00:00
abstract::The Na+/Ca2+ exchanger plays an important role in the maintenance of calcium homeostasis in the heart. Therefore, factors which regulate the exchanger have a significant impact on cardiac function. Previously, we showed that the non-hydrolysable GTP analog, 5'guanylyl imidodiphosphate [Gpp(NH)p], stimulates Na+/Ca2+ e...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1996.0002
更新日期:1996-01-01 00:00:00
abstract::The agent 2,3-butanedione monoxime (BDM) has been reported to reduce the sensitivity of myofilament force development to calcium ions, without affecting the calcium transient in myocardium. One would predict, therefore, that BDM should reduce the contractile state of the heart without reducing the amount of oxygen tha...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)91093-k
更新日期:1992-08-01 00:00:00
abstract::Wide variation exists in the extent (number and diameter) of native pre-existing collaterals in tissues of different strains of mice, with supportive indirect evidence recently appearing for humans. This variation is a major determinant of the wide variation in severity of tissue injury in occlusive vascular disease. ...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2015.07.020
更新日期:2015-10-01 00:00:00
abstract::The biological function of FAM3A, the first member of family with sequence similarity 3 (FAM3) gene family, remains largely unknown. This study aimed to determine its role in the proliferation and migration of vascular smooth muscle cells (VSMCs). Immunohistochemical staining revealed that FAM3A protein is expressed i...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2014.05.011
更新日期:2014-09-01 00:00:00
abstract::In this study, we looked into possible compensatory changes of other adenosine receptors (ARs) in A(2A) genetic knockout mice (A2AKO) as well as the functional role of nitric oxide (NO) in A(2A) AR-mediated vasodilation. Gene expression of ARs from coronary arteries of A(2A) AR wild type mice (A2AWT) and A2AKO was stu...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.003
更新日期:2008-05-01 00:00:00
abstract::This study addresses the role of polyamines and their rate limiting enzyme, ornithine decarboxylase in regulation of macromolecular transport of two macromolecules, fluorescein and horseradish peroxidase, across coronary capillaries. Rat hearts were isolated and retrogradely perfused through the aorta (Langendorff met...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1994.1046
更新日期:1994-03-01 00:00:00
abstract::The atrioventricular conduction axis, located in the septal component of the atrioventricular junctions, is arguably the most complex structure in the heart. It fulfils a multitude of functions, including the introduction of a delay between atrial and ventricular systole and backup pacemaking. Like any other multifunc...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2010.12.017
更新日期:2011-04-01 00:00:00
abstract::Carnitine, certain of its derivatives, and the amino acid metabolite, taurine, when administered independently in prior studies have been shown to improve cardiac mechanic and/or metabolism. The purpose of these studies is to test a new compound, propionylcarnitine taurine (PCT), which potentially combines these actio...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/s0022-2828(88)80179-2
更新日期:1988-01-01 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::With a research hypothesis that the behavior of blood perfused hearts was different from that of crystalloid perfused hearts, we tested the null hypothesis that the functional and metabolic status of blood-perfused (paracorporeal oxygenation) and Krebs-Henseleit (bubble oxygenation) perfused Langendorff isolated rat h...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(92)93172-g
更新日期:1992-10-01 00:00:00
abstract::The cardiac renin-angiotensin system (RAS) has been implicated in mediating myocyte hypertrophy, remodeling, and fibroblast proliferation in the hemodynamically overloaded heart. However, the intracellular signaling mechanisms responsible for regulation of angiotensinogen (Ao), a substrate of the RAS system, are large...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.09.121
更新日期:2008-12-01 00:00:00
abstract::Cardiac myosin-binding protein C (cMyBP-C) is a component of the thick filaments of the sarcomere. Understanding the structural and functional role of cMyBP-C in the heart is clinically relevant since cMyBP-C gene mutations are a widely recognized cause of hypertrophic cardiomyopathy (HCM), which affects 0.2% of the g...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.yjmcc.2011.01.014
更新日期:2011-04-01 00:00:00
abstract::Since ascorbate is unnecessary for cell growth and survival, cardiac fibroblasts are routinely cultured without it. However, ascorbate is necessary for optimal collagen synthesis, so we hypothesized that its presence would influence cell phenotype. Cardiac fibroblasts cultured without ascorbate had increased intracell...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2017.09.005
更新日期:2017-12-01 00:00:00
abstract::Arterial hypotension can cause cerebral ischemia when the autoregulation of the cerebral circulation is exhausted. We hypothesized that sudden cerebral vasoconstriction induced by moderate hypotensive, but hemodynamically stable, sustained ventricular tachycardias (MHT-VT) further compromises cerebral blood flow (CBF)...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0772
更新日期:1998-10-01 00:00:00
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::(±)-Sodium5-bromo-2-(α-hydroxypentyl) benzoate (brand name: brozopine, BZP, 1a), derived from L-3-n-butylphthalide (L-NBP), has been reported to protect the brain from stoke and has been approved by CFDA in Phase I-II clinical trials. However, it remains to be investigated whether 1a may exhibit any cardioprotective e...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2019.07.014
更新日期:2019-10-01 00:00:00
abstract::In the human heart connexin(Cx)40, Cx43 and Cx45-containing gap junctional channels electrically couple cardiomyocytes, forming a functional syncytium. In the mouse heart, additionally, Cx30.2-containing gap junctions have been detected in the atrioventricular node where they are implicated, together with Cx45, in imp...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.12.007
更新日期:2009-04-01 00:00:00
abstract::Screening for cell surface proteins up-regulated under stress conditions may lead to the identification of new therapeutic targets. To search for genes whose expression was enhanced by treatment with oligomycin, a mitochondrial-F(0)F(1) ATP synthase inhibitor, signal sequence trapping was performed in H9C2 rat cardiac...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2009.10.014
更新日期:2010-06-01 00:00:00
abstract::We studied the presence of collagen degrading enzymes (matrix metalloproteinases, MMPs) in porcine myocardium following ischemia and late reperfusion. In nine pigs, left anterior descending coronary artery was occluded for 6 h followed by reperfusion for 3 h. Six pigs without coronary occlusion served as controls. Aft...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1998.0711
更新日期:1998-07-01 00:00:00
abstract::The heart contains many cell types; mechanical work is done by cardiomyocytes which do not divide but are terminally differentiated and capable of continuous protein synthesis and degradation. The steps in protein synthesis are (1) transport of amino acids into heart cells by a variety of cell-membrane carriers, (2) A...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章,评审
doi:10.1016/s0022-2828(84)80711-7
更新日期:1984-01-01 00:00:00
abstract::The mechanism of the antiadrenergic action of adenosine in the heart was investigated by examining the effects of phenylisopropyladenosine (PIA), an adenosine A1 receptor agonist, on beta-adrenergic receptor and non-receptor elicited increases in adenylyl cyclase activity of guinea-pig ventricular membranes. These mem...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/0022-2828(90)90981-7
更新日期:1990-12-01 00:00:00
abstract::The effects of Cobra venom cardiotoxin (CTX) on the cellular morphology, twitch amplitude and intracellular calcium ([Ca2+]i) of the ventricular myocytes were studied. [Ca2+]i and twitch amplitude were determined with a fluorometric ratio method using Fura-2/AM and Calcium Green-1 as calcium indicators, and a videomic...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.1997.0511
更新日期:1997-10-01 00:00:00
abstract::The goal of this study was to test the hypothesis that the novel anti-ischemic drug ranolazine, which is known to inhibit late I(Na), could reduce intracellular [Na(+)](i) and diastolic [Ca(2+)](i) overload and improve diastolic function. Contractile dysfunction in human heart failure (HF) is associated with increased...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1016/j.yjmcc.2008.03.006
更新日期:2008-07-01 00:00:00
abstract::Short duration exposure to cellular stresses have been shown to activate p38 mitogen-activated protein kinase (MAPK) in cultured rat ventricular cardiomyocytes and isolated perfused hearts; however, effects of chronic stress on p38 MAPK are not well understood. This study determined whether alterations in the p38 MAPK...
journal_title:Journal of molecular and cellular cardiology
pub_type: 杂志文章
doi:10.1006/jmcc.2001.1415
更新日期:2001-08-01 00:00:00