Abstract:
:Cellular Ca2+ regulation is abnormal in diseased hearts. We designed this study to assess the role of the Na(+)-Ca2+ exchanger in excitation-contraction coupling in surviving myocardium of the infarcted heart. We measured cellular contractions and whole-cell currents in single left ventricular myocytes isolated from the hearts of rabbits with healed myocardial infarction (MI). Eight weeks after MI, rabbits had left ventricular dysfunction without overt heart failure. Myocytes isolated from regions adjacent to the infarcted zone were significantly longer than cells from control hearts. At low stimulation rates (0.5 Hz), the amplitude of field-stimulated contractions was increased (11.6 +/- 0.5% versus 10.2 +/- 0.6% resting cell length), whereas the time to peak shortening and action potential duration were prolonged in the MI cells. When stimulation frequency was increased to 2.0 Hz, cellular shortening did not change or decreased in myocytes from infarcted hearts, whereas control cells had a positive shortening-interval relationship. Cells from infarcted hearts had a significantly decreased (31%) L-type Ca2+ current (ICa) density but no change in the current-voltage relationship or the kinetics of ICa inactivation. Maximal Na(+)-Ca2+ exchange current density was significantly increased (32%) in the cells from infarcted hearts. Sarcoplasmic reticulum (SR) Ca2+ content during a stable train of contractions, as estimated from caffeine-induced inward currents, was slightly increased (P = NS) in the MI myocytes. To determine whether Na(+)-Ca2+ exchange influenced SR Ca2+ content, cells were clamped at potentials between -70 and +90 mV for 400 ms. The amplitude of the contraction during a subsequent clamp step to +10 mV was then measured as an index of SR loading that occurred during the preceding clamp step. Steps to positive potentials produced greater augmentation of the subsequent contraction in MI than in control myocytes. In myocytes from the infarcted heart, increased activity of the Na(+)-Ca2+ exchanger may promote Ca2+ entry or decrease Ca2+ extrusion. This relative augmentation of inward Ca2+ flux by the exchanger may enhance SR Ca2+ loading and thus support contractility that would otherwise be impaired as a result of decreased Ca2+ current. However, Ca2+ influx by the exchanger may contribute to the prolongation of contractions in myocytes from infarcted hearts.
journal_name
Circ Resjournal_title
Circulation researchauthors
Litwin SE,Bridge JHdoi
10.1161/01.res.81.6.1083subject
Has Abstractpub_date
1997-12-01 00:00:00pages
1083-93issue
6eissn
0009-7330issn
1524-4571journal_volume
81pub_type
杂志文章abstract::Although functional coupling between protein kinase Cepsilon (PKCepsilon) and mitochondria has been implicated in the genesis of cardioprotection, the signal transduction mechanisms that enable this link and the identities of the mitochondrial proteins modulated by PKCepsilon remain unknown. Based on recent evidence t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000069215.36389.8D
更新日期:2003-05-02 00:00:00
abstract::Pinocytotic vesicles are one of several anatomic factors relevant to the permeability for macromolecules of capillary endothelia. We quantitified the number and distribution of pinocytotic vesicles present in the endothelium of pulmonary capillaries. Several similar studies have been reported in the past for endotheli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.47.3.384
更新日期:1980-09-01 00:00:00
abstract::Calcific aortic valve sclerosis involves inflammatory processes and occurs preferentially on the aortic side of endothelialized valve leaflets. Although the endothelium is recognized to play critical roles in focal vascular sclerosis, the contributions of valvular endothelial phenotypes to aortic valve sclerosis and s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000161998.92009.64
更新日期:2005-04-15 00:00:00
abstract::Matrix metalloproteinases (MMPs) include most major constituents of the arterial wall as substrates. A common promotor polymorphism (5A/6A) is associated with differences in MMP-3 (stromelysin-1) activity, and associations with certain forms of vascular disease have been shown. This study investigated whether the MMP-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000076891.24317.CA
更新日期:2003-06-13 00:00:00
abstract::Endothelial cells isolated from bovine aortas without prior treatment with enzymes were cultured in RPMI 1640 medium containing 17% fetal calf serum and antibiotics. The endothelial cells at confluency (7 days) were similar to endothelium in situ or to freshly isolated endothelial cells from blood vessels as seen by l...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.799
更新日期:1975-06-01 00:00:00
abstract::This report evaluates pulse wave propagation with respect to contributions by vascular wall elastic and geometric properties, vessel wall and blood viscosity, and nonlinearities in system parameters and in the equations of motion. Discrepancies in results obtained with different experimental methods and theory are dis...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.49.2.442
更新日期:1981-08-01 00:00:00
abstract::Calcium channel blockers (CCBs), which are used clinically for treatment of angina and hypertension, are known to inhibit calcium influx into arterial smooth muscle cells and thereby decrease smooth muscle cell contraction. In addition, they prevent cholesteryl ester (CE) accumulation, the hallmark of human atheroscle...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.1.185
更新日期:1990-01-01 00:00:00
abstract::In vivo studies of the rheological behavior of blood in the microcirculation were conducted by direct in situ measurements in cat mesentery. Upstream to downstream pressure drops were measured in unbranched arterioles, capillaries, and venules, with diameters from 7 to 58 micrometer. Simultaneous measurements of red c...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.43.5.738
更新日期:1978-11-01 00:00:00
abstract::The purpose of this study was to determine whether a quantitative relationship existed between a reduction in regional myocardial blood flow, measured by radiolabeled microspheres, and the degree and type of changes in myocardial activation recorded in bipolar left ventricular subepicardial and subendocardial electrog...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.45.6.764
更新日期:1979-12-01 00:00:00
abstract::Proliferation of vascular smooth muscle cells (VSMC) is a primary cause of vascular disorders and is associated with major alterations in Ca2+ handling supported by loss of the sarco/endoplasmic reticulum calcium ATPase, SERCA2a. To determine the importance of SERCA2a in neointima formation, we have prevented loss of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000180663.42594.aa
更新日期:2005-09-02 00:00:00
abstract::A distal transcriptional enhancer has been previously reported upstream of the mouse renin gene. A homologous sequence is also present upstream of the human renin gene, but the mouse and human renin enhancers differ markedly in their ability to activate transcription of a renin promoter. Although the 2 enhancers share...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.6.479
更新日期:1999-09-17 00:00:00
abstract:RATIONALE:Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biolo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.302476
更新日期:2014-04-25 00:00:00
abstract::The spatial and dynamic properties of ventricular fibrillation (VF) may be random or related to cellular electrical properties of the normal heart. Local activation intervals (AIs) in VF may depend on the local refractory period (RP), and sustained VF may require a steep action potential (AP) restitution curve. In gui...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.5.e49
更新日期:2001-03-16 00:00:00
abstract::Multiple voltage-gated K+ channels contribute to the repolarization phases of the cardiac action potential and are targets of several antiarrhythmic drugs. The Kv1.5 K+ channel gene is expressed in the heart, and heterologous expression of this gene generates a slowly inactivating K+ current. Previously, we found that...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.6.1006
更新日期:1994-12-01 00:00:00
abstract::This article examines the role of innervation in regulating expression of acetylcholinesterase (AchE), butyrylcholinesterase (BuchE), and the muscarinic acetylcholine receptor (mAchR) in avian heart. Two distinct approaches are taken. The first approach examines the relation between the onsets of parasympathetic and s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.4.633
更新日期:1992-04-01 00:00:00
abstract:RATIONALE:Cardiac resynchronization therapy (CRT) is an effective clinical treatment for heart failure patients with conduction delay, impaired contraction, and energetics. Our recent studies have revealed that mitochondrial posttranslational modifications (PTM) may contribute to its benefits, motivating the present st...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.246124
更新日期:2011-09-16 00:00:00
abstract::Ectopic calcification of blood vessels, heart valves, and skeletal muscle is a major clinical problem. There is now good evidence that angiogenesis is associated with ectopic calcification in these tissues and that it is necessary, but not sufficient, for calcification to occur. Angiogenesis may regulate ectopic calci...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000163634.51301.0d
更新日期:2005-05-13 00:00:00
abstract::The possibility of an interaction between the cytoskeletal protein dystrophin and cell surface caveolae in the mammalian myocardium was investigated by several techniques. Caveolin (cav)-3-enriched, detergent-insoluble membranes isolated from purified ventricular sarcolemma by density-gradient fractionation were found...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.6.480
更新日期:2000-09-15 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::This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during var...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.9.768
更新日期:2000-10-27 00:00:00
abstract:RATIONALE:The mechanisms driving atherothrombotic risk in individuals with JAK2 V617F ( Jak2 VF) positive clonal hematopoiesis or myeloproliferative neoplasms are poorly understood. OBJECTIVE:The goal of this study was to assess atherosclerosis and underlying mechanisms in hypercholesterolemic mice with hematopoietic ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313283
更新日期:2018-11-09 00:00:00
abstract::Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia-inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF-1 activity depends on the amount of HIF-1alpha subunit, which is tightly regulated by the oxygen tension. In the myocardium, VEGF expression has been shown to ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0202.104923
更新日期:2002-02-08 00:00:00
abstract::Vessel stabilization and the inhibition of side effects such as tissue edema are essential in angiogenic gene therapy. Thus, combination gene transfers stimulating both endothelial cell and pericyte proliferation have become of interest. However, there is currently little data to support combination gene transfer in l...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.182287
更新日期:2008-11-07 00:00:00
abstract::Large conductance Ca(2+)-activated K(+) channels (BK(Ca)) play a critical role in blood pressure regulation by tuning the vascular smooth muscle tone, and hyposensitivity of BK(Ca) to Ca(2+) sparks resulting from its altered beta1 subunit stoichiometry underlies vasoconstriction in animal models of hypertension. Here ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.157271
更新日期:2007-08-31 00:00:00
abstract::Studies were performed to characterize the morphology and vascular reactivity of the allografted cerebral microcirculation. Cerebral cortical tissue was allografted into the cheek pouch of the hamster so that cerebral parenchymal vessels could be studied. The vascular morphology was characterized by a large number of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.4.758
更新日期:1988-10-01 00:00:00
abstract:RATIONALE:Post-myocardial infarction ventricular remodeling is associated with the expression of a variety of factors including S100B that can potentially modulate myocyte apoptosis. OBJECTIVE:This study was undertaken to investigate the expression and function of S100B and its receptor, the receptor for advanced glyc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.195834
更新日期:2010-01-08 00:00:00
abstract::The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000059562.91384.1A
更新日期:2003-03-07 00:00:00
abstract::Peroxisome proliferator-activated receptor (PPAR) gamma is activated by thiazolidinediones (TZDs), widely used as insulin-sensitizing agents for the treatment of type 2 diabetes. TZDs have been shown to induce apoptosis in a variety of mammalian cells. In vascular smooth muscle cells (VSMCs), proliferation and apoptos...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000088344.15288.E6
更新日期:2003-08-22 00:00:00
abstract::Fcγ receptors (FcγRs) classically modulate intracellular signaling on binding of the Fc region of IgG in immune response cells. How FcγR and their ligands affect cardiovascular health and disease has been interrogated recently in both preclinical and clinical studies. The stimulation of activating FcγR in endothelial ...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.302795
更新日期:2015-01-16 00:00:00
abstract::The purpose of these experiments was to determine whether or not acetylcholine modulated the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers. Conventional microelectrode techniques were used. Predictably, isoproterenol produced shortening of action potential duration; acetylcholine sign...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.3.378
更新日期:1979-03-01 00:00:00