Abstract:
:Excitation-contraction coupling in the cardiac myocyte is mediated by a number of highly integrated mechanisms of intracellular Ca²(+) transport. The complexity and integrative nature of heart cell electrophysiology and Ca²(+) cycling has led to an evolution of computational models that have played a crucial role in shaping our understanding of heart function. An important emerging theme in systems biology is that the detailed nature of local signaling events, such as those that occur in the cardiac dyad, have important consequences at higher biological scales. Multiscale modeling techniques have revealed many mechanistic links between microscale events, such as Ca²(+) binding to a channel protein, and macroscale phenomena, such as excitation-contraction coupling gain. Here, we review experimentally based multiscale computational models of excitation-contraction coupling and the insights that have been gained through their application.
journal_name
Circ Resjournal_title
Circulation researchauthors
Greenstein JL,Winslow RLdoi
10.1161/CIRCRESAHA.110.223578subject
Has Abstractpub_date
2011-01-07 00:00:00pages
70-84issue
1eissn
0009-7330issn
1524-4571pii
108/1/70journal_volume
108pub_type
杂志文章,评审abstract::In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.1.33
更新日期:1994-07-01 00:00:00
abstract:RATIONALE:Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.204891
更新日期:2010-03-19 00:00:00
abstract::Brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) are novel natriuretic peptides, originally isolated from porcine brain. Similar to atrial natriuretic peptide (ANP), BNP is also synthesized in and secreted from cardiocytes, but CNP is not expressed at significant levels in normal adult myocardium. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.1.9
更新日期:1992-07-01 00:00:00
abstract::We have shown that the cellular contractile dysfunction characteristic of pressure-overload cardiac hypertrophy results not from an abnormality intrinsic to the myofilament portion of the cardiocyte cytoskeleton but rather from an increased density of the microtubule component of the extramyofilament portion of the ca...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.2.281
更新日期:1997-02-01 00:00:00
abstract::Congenital heart defects affect almost 1% of human newborns. Recently, mutations in Notch ligands and receptors have been found to cause a variety of heart defects in rodents and humans. However, the molecular effects downstream of Notch are still poorly understood. Here we report that combined inactivation of Hey1 an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000260913.95642.3b
更新日期:2007-03-30 00:00:00
abstract::The purpose of this study was to determine whether increased sympathetic nervous system activity with proportionally greater stimulation to the kidney could result in sustained hypertension. This was simulated by continuous intrarenal norepinephrine infusion. Effects of chronic infusion of norepinephrine (0.285 micron...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1977-05-01 00:00:00
abstract:RATIONALE:The dramatic upregulation of αvβ3-integrin that occurs in the vasculature during tumor growth has long suggested that the endothelial expression of this molecule is an ideal target for antiangiogenic therapy to treat cancer. This discovery led to the development of small-molecule inhibitors directed against α...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.301591
更新日期:2014-01-03 00:00:00
abstract:RATIONALE:Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. OBJECTIVE:To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. METHODS AND RESULTS:We studied 538 CHD trios using genome-wide dense single nucle...
journal_title:Circulation research
pub_type: 临床试验,杂志文章
doi:10.1161/CIRCRESAHA.115.304458
更新日期:2014-10-24 00:00:00
abstract::Cardiac failure appears rapidly during severe hypoxia and precedes a substantial reduction in adenosine triphosphate content. Reduced adenosine triphosphate turnover, in the presence of nearly normal content, may be the metabolic basis for contractile failure during hypoxia. To measure both the myocardial content and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.6.871
更新日期:1987-06-01 00:00:00
abstract::Among the factors that might influence collateral arterial growth after arterial occlusion, the capacity to deliver blood flow in relation to metabolic need and work performance are obvious candidates. In this study in rats after superficial femoral artery ligation, we assessed collateral arterial growth (by arteriogr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.3.546
更新日期:1992-03-01 00:00:00
abstract::We have shown previously that tyrosine 319 in a conserved YIPP motif in the C terminus of angiotensin II (Ang II) type 1 receptors (AT(1)Rs) is essential for transactivation of epidermal growth factor receptor (EGFR) in vitro. We hypothesized that the signaling mechanism mediated through the specific amino acid sequen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000240147.49390.61
更新日期:2006-09-01 00:00:00
abstract::The functional disturbance of microvasculature is recognized as an initiating mechanism that underlies the development of various diabetic complications. Although a causal relationship between microvascular leakage and tissue damage has been well documented in diabetic kidneys and eyes, there is a lack of information ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.5.412
更新日期:2000-09-01 00:00:00
abstract::The mechanism(s) by which mutations in sarcomeric proteins cause hypertrophic cardiomyopathy (HCM) remains unknown. A leading hypothesis proposes that mutant sarcomeric proteins impair cardiac myocyte contractility, providing an impetus for compensatory hypertrophy. To test this hypothesis, we determined the impact of...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.1.76
更新日期:1997-07-01 00:00:00
abstract::Understanding the molecular interactions among components of cardiac Z-discs and their role in signaling has become pivotal in explaining long- and short-term regulation of cardiac function. In striated muscle, the ends of the thin filaments from opposing sarcomeres overlap and are cross-linked by an elaborate array o...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000116143.74830.A9
更新日期:2004-02-20 00:00:00
abstract::The signaling pathways involved in the long-term metabolic effects of angiotensin II (Ang II) in vascular smooth muscle cells are incompletely understood but include the generation of molecules likely to affect oxidase activity. We examined the ability of Ang II to stimulate superoxide anion formation and investigated...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.6.1141
更新日期:1994-06-01 00:00:00
abstract:RATIONALE:Uncoupling protein (UCP)2 is a mitochondrial inner membrane protein that is expressed in mammalian myocardium under normal conditions and upregulated in pathological states such as heart failure. UCP2 is thought to protect cardiomyocytes against oxidative stress by dissipating the mitochondrial proton gradien...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206631
更新日期:2010-03-05 00:00:00
abstract::Heart failure (HF) has been singled out as an epidemic and is a staggering clinical and public health problem, associated with significant mortality, morbidity, and healthcare expenditures, particularly among those aged ≥ 65 years. The case mix of HF is changing over time with a growing proportion of cases presenting ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300268
更新日期:2013-08-30 00:00:00
abstract::In clinical trials, aldosterone antagonists decrease cardiovascular mortality and ischemia by unknown mechanisms. The steroid hormone aldosterone acts by binding to the mineralocorticoid receptor (MR), a ligand-activated transcription factor. In humans, aldosterone causes MR-dependent endothelial cell (EC) dysfunction...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.174235
更新日期:2008-06-06 00:00:00
abstract::To investigate the contributions of humoral and hemodynamic factors to cardiac adaptations associated with chronic exercise, female Fischer 344 rats were subjected to chronic swimming, infrarenal cardiac transplantation, or both. Swimming resulted in hypertrophy (11-12%) of the in situ hearts in both the unoperated an...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.3.780
更新日期:1990-09-01 00:00:00
abstract::The plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude equal to or less than 5% Lmax) was obtained. Isotonic oscillations were less damped than their isom...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.38.4.289
更新日期:1976-04-01 00:00:00
abstract::Electrical propagation in the normal heart occurs via intercellular transfer of current at gap junctions. Alterations in intercellular coupling in the diseased heart are critical in the pathogenesis of reentrant ventricular arrhythmias. Until recently only a single gap junction protein was known to couple cardiac myoc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.438
更新日期:1992-02-01 00:00:00
abstract::The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during ce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.5.966
更新日期:1993-05-01 00:00:00
abstract::The relationship of P-wave polarity and morphology in leads II, III, and aVF to the sequence of atrial activation was studied in the canine heart when the atria were paced from the region of the sinus node or the posterior-inferior left atrium and when retrograde activation of the atria occurred with right ventricular...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.2.156
更新日期:1975-08-01 00:00:00
abstract::Voltage-gated L-type Ca(2+) channels (LCCs) provide Ca(2+) ingress into cardiac myocytes and play a key role in intracellular Ca(2+) homeostasis and excitation-contraction coupling. We investigated the effects of a constitutive increase of LCC density on Ca(2+) signaling in ventricular myocytes from 4-month-old transg...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0202.103230
更新日期:2002-02-08 00:00:00
abstract::Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses fo...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300269
更新日期:2013-08-30 00:00:00
abstract::We determined whether local bradykinin production modulates cardiac adrenergic activity. Depolarization of guinea pig heart sympathetic nerve endings (synaptosomes) with 1 to 100 mmol/L K+ caused the release of endogenous norepinephrine (10% to 50% above basal level). This release was exocytotic, because it depended o...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.5.774
更新日期:1997-11-01 00:00:00
abstract:RATIONALE:The peptide ligand apelin and its receptor APJ constitute a signaling pathway with numerous effects on the cardiovascular system, including cardiovascular development in model organisms such as xenopus and zebrafish. OBJECTIVE:This study aimed to characterize the embryonic lethal phenotype of the Apj-/- mice...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301324
更新日期:2013-06-21 00:00:00
abstract::Oxidized phospholipids, including oxidation products of palmitoyl-arachidonyl-phosphatidyl choline (PAPC), are mediators of inflammation in endothelial cells (ECs) and known to induce several chemokines, including interleukin-8 (IL-8). In this study, we show that oxidized PAPC (OxPAPC), which accumulates in atheroscle...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000146030.53089.18
更新日期:2004-10-15 00:00:00
abstract::To determine whether the vasoconstriction evoked by A1-adenosine receptor stimulation in the skin circulation caused the release of other substances or whether A1 stimulation modulated the vasoconstriction evoked by other compounds, a potent A1-selective, synthetic agonist, cyclohexyladenosine (CHA), was topically app...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.3.683
更新日期:1991-03-01 00:00:00
abstract:RATIONALE:During the transition from compensated hypertrophy to heart failure, the signaling between L-type Ca(2+) channels in the cell membrane/T-tubules and ryanodine receptors in the sarcoplasmic reticulum becomes defective, partially because of the decreased expression of a T-tubule-sarcoplasmic reticulum anchoring...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.300806
更新日期:2013-02-15 00:00:00