Transmural heterogeneity of Na+-Ca2+ exchange: evidence for differential expression in normal and failing hearts.

Abstract:

:Spatial electrical heterogeneity has a profound effect on normal cardiac electrophysiology and genesis of cardiac arrhythmias in diseased hearts. The Na+-Ca2+ exchanger (NCX) is a key linker, through Ca2+ signaling, between contractility and arrhythmias. Here we characterize the differential transmural expression of NCX in normal and rapid pacing-induced failing canine hearts. Significant transmural heterogeneity of NCX was present in normal hearts, as NCX current density measured at +80 mV was significantly (P<0.05) greater in epicardial (EPI) (5.49 pA/pF) than mid-myocardial (MID) (2.84 pA/pF) and endocardial (ENDO) (2.21 pA/pF) cells. Interestingly, heart failure caused a selective increase in NCX current density (P<0.05) limited to ENDO (by 202%) and MID (by 76%) but not EPI myocytes (P=not significant). The differences in functional expression were associated with changes in both mRNA and protein levels. The normal EPI layer exhibited the greatest NCX mRNA and protein levels compared with MID and ENDO layers, whereas the ENDO layer underwent the most pronounced increase in mRNA (by 185%) and protein (by 207%) levels in heart failure. The transmural NCX gradient, from EPI (greatest) to ENDO (least), is disrupted in heart failure. A selective upregulation of NCX expression in MID and ENDO in heart failure markedly redirects the orientation of the transmural functional gradient of NCX and may lead to enhanced vulnerability to cardiac arrhythmias.

journal_name

Circ Res

journal_title

Circulation research

authors

Xiong W,Tian Y,DiSilvestre D,Tomaselli GF

doi

10.1161/01.RES.0000175935.08283.27

subject

Has Abstract

pub_date

2005-08-05 00:00:00

pages

207-9

issue

3

eissn

0009-7330

issn

1524-4571

pii

01.RES.0000175935.08283.27

journal_volume

97

pub_type

杂志文章
  • Input impedance of the lower abdominal aorta in chronically instrumented fetal sheep.

    abstract::Five fetal sheep (gestational age, 118 to 125 days) were instrumented to measure impedances of the lower abdominal aorta. Four days after surgery, flow and pressure pulses were recorded during control conditions and during infusion of norepinephrine (0.3 to 3 micrograms.min-1.kg-1 body weight) or angiotensin II (0.2 t...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.74.4.641

    authors: Schröder H,Cetin E,Hüneke B,Carstensen M

    更新日期:1994-04-01 00:00:00

  • miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling.

    abstract::The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosis. Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an att...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.108.182535

    authors: Duisters RF,Tijsen AJ,Schroen B,Leenders JJ,Lentink V,van der Made I,Herias V,van Leeuwen RE,Schellings MW,Barenbrug P,Maessen JG,Heymans S,Pinto YM,Creemers EE

    更新日期:2009-01-30 00:00:00

  • In Situ Expansion, Differentiation, and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.

    abstract:RATIONALE:One goal of cardiac tissue engineering is the generation of a living, human pump in vitro that could replace animal models and eventually serve as an in vivo therapeutic. Models that replicate the geometrically complex structure of the heart, harboring chambers and large vessels with soft biomaterials, can be...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.119.316155

    authors: Kupfer ME,Lin WH,Ravikumar V,Qiu K,Wang L,Gao L,Bhuiyan DB,Lenz M,Ai J,Mahutga RR,Townsend D,Zhang J,McAlpine MC,Tolkacheva EG,Ogle BM

    更新日期:2020-07-03 00:00:00

  • Cod liver oil alters platelet-arterial wall response to injury in pigs.

    abstract::In 36 normolipemic pigs randomized to a 4-week feeding with regular pig chow (n = 18, control group) or chow supplemented with cod liver oil (1 ml/kg per day) (n = 18, treated group), treatment with cod liver oil produced a significant decrease in serum cholesterol, low density lipoprotein cholesterol, and triglycerid...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.71.4.769

    authors: Lam JY,Badimon JJ,Ellefson RD,Fuster V,Chesebro JH

    更新日期:1992-10-01 00:00:00

  • Vascular remodeling and improvement of coronary reserve after hydralazine treatment in spontaneously hypertensive rats.

    abstract::The purpose of these studies was to evaluate cardiovascular structural and functional changes in a model of hypertension-induced myocardial hypertrophy in which vasodilator therapy decreased blood pressure to normal levels. Thus, we determined the separate contributions of hypertension and hypertrophy on myocardial an...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.64.6.1127

    authors: Anderson PG,Bishop SP,Digerness SB

    更新日期:1989-06-01 00:00:00

  • Species-specific differences in positive and negative regulatory elements in the renin gene enhancer.

    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

    authors: Shi Q,Black TA,Gross KW,Sigmund CD

    更新日期:1999-09-17 00:00:00

  • A central mechanism of acute baroreflex resetting in the conscious dog.

    abstract::The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the le...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.1.63

    authors: Tan W,Panzenbeck MJ,Hajdu MA,Zucker IH

    更新日期:1989-07-01 00:00:00

  • Calcium channels in muscle cells isolated from rat mesenteric arteries: modulation by dihydropyridine drugs.

    abstract::The patch clamp technique was used to make whole-cell recordings of calcium channel currents from single muscle cells freshly isolated from rat mesenteric arteries. The cells were found to contain two types of calcium channels; one type is activated by small depolarizations and inactivates quickly, whereas the other r...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.59.2.229

    authors: Bean BP,Sturek M,Puga A,Hermsmeyer K

    更新日期:1986-08-01 00:00:00

  • Effects of damaging the endocardial surface on the mechanical performance of isolated cardiac muscle.

    abstract::The mechanical properties of mammalian ventricular cardiac muscle have been studied in the presence and in the absence of an intact endocardial surface. Isotonic and isometric twitch contractions were obtained from papillary muscles of the right ventricle of cat at 29 degrees and 37 degrees C, at different extracellul...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.62.2.358

    authors: Brutsaert DL,Meulemans AL,Sipido KR,Sys SU

    更新日期:1988-02-01 00:00:00

  • Novel pharmacophores of connexin43 based on the "RXP" series of Cx43-binding peptides.

    abstract::Gap junction pharmacology is a nascent field. Previous studies have identified molecules that enhance intercellular communication, and may offer potential for innovative antiarrhythmic therapy. However, their specific molecular target(s) and mechanism(s) of action remain unknown. Previously, we identified a 34-aa pept...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.109.200576

    authors: Verma V,Larsen BD,Coombs W,Lin X,Spagnol G,Sorgen PL,Taffet SM,Delmar M

    更新日期:2009-07-17 00:00:00

  • Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy.

    abstract::To determine the effects of aging on the human myocardium, 67 hearts were obtained from individuals who died from causes other than cardiovascular disease. The age interval examined was 17-90 years. Regression analysis demonstrated that the aging process was characterized by a loss of 38 million and 14 million myocyte...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.68.6.1560

    authors: Olivetti G,Melissari M,Capasso JM,Anversa P

    更新日期:1991-06-01 00:00:00

  • Oxidative stress-dependent sphingosine kinase-1 inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis.

    abstract::The mitochondrial enzyme monoamine oxidase (MAO), its isoform MAO-A, plays a major role in reactive oxygen species-dependent cardiomyocyte apoptosis and postischemic cardiac damage. In the current study, we investigated whether sphingolipid metabolism can account for mediating MAO-A- and reactive oxygen species-depend...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000253900.66640.34

    authors: Pchejetski D,Kunduzova O,Dayon A,Calise D,Seguelas MH,Leducq N,Seif I,Parini A,Cuvillier O

    更新日期:2007-01-05 00:00:00

  • Bone marrow mononuclear cell therapy for acute myocardial infarction: a perspective from the cardiovascular cell therapy research network.

    abstract::To understand the role of bone marrow mononuclear cells in the treatment of acute myocardial infarction, this overview offers a retrospective examination of strengths and limitations of 3 contemporaneous trials with attention to critical design features and provides an analysis of the combined data set and implication...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCRESAHA.114.303720

    authors: Simari RD,Pepine CJ,Traverse JH,Henry TD,Bolli R,Spoon DB,Yeh E,Hare JM,Schulman IH,Anderson RD,Lambert C,Sayre SL,Taylor DA,Ebert RF,Moyé LA

    更新日期:2014-05-09 00:00:00

  • Local monocyte chemoattractant protein-1 therapy increases collateral artery formation in apolipoprotein E-deficient mice but induces systemic monocytic CD11b expression, neointimal formation, and plaque progression.

    abstract::Monocyte chemoattractant protein-1 (MCP-1) stimulates the formation of a collateral circulation on arterial occlusion. The present study served to determine whether these proarteriogenic properties of MCP-1 are preserved in hyperlipidemic apolipoprotein E-deficient (apoE-/-) mice and whether it affects the systemic de...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.0000052313.23087.3f

    authors: van Royen N,Hoefer I,Böttinger M,Hua J,Grundmann S,Voskuil M,Bode C,Schaper W,Buschmann I,Piek JJ

    更新日期:2003-02-07 00:00:00

  • Epidemiology of heart failure.

    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

    authors: Roger VL

    更新日期:2013-08-30 00:00:00

  • Beat-by-Beat Cardiomyocyte T-Tubule Deformation Drives Tubular Content Exchange.

    abstract:RATIONALE:The sarcolemma of cardiomyocytes contains many proteins that are essential for electromechanical function in general, and excitation-contraction coupling in particular. The distribution of these proteins is nonuniform between the bulk sarcolemmal surface and membrane invaginations known as transverse tubules ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.317266

    authors: Rog-Zielinska EA,Scardigli M,Peyronnet R,Zgierski-Johnston CM,Greiner J,Madl J,O'Toole ET,Morphew M,Hoenger A,Sacconi L,Kohl P

    更新日期:2021-01-22 00:00:00

  • Stress, deformation, and atelectasis of the lung.

    abstract::The lung parenchyma as a tissue has a rather unusual stress-strain relationship. A theoretical derivation of this relationship is presented which connects the surface tension and the tissue elastic stress in the alveolar septa with the alveolar geometry. The mathematical expression contains a few meaningful physical c...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.37.4.481

    authors: Fung YC

    更新日期:1975-10-01 00:00:00

  • Distinct receptors and signaling pathways in alpha-thrombin- and thrombin receptor peptide-induced vascular contractions.

    abstract::The vasoactive mechanisms of the serine protease alpha-thrombin were examined in isolated coronary arteries from dogs. In resting coronary arteries with endothelium, alpha-thrombin caused concentration-dependent contractions that were characterized by an initial transient relaxation followed by slowly developing susta...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.74.5.930

    authors: Tesfamariam B

    更新日期:1994-05-01 00:00:00

  • Duration and Life-Stage of Antibiotic Use and Risks of All-Cause and Cause-Specific Mortality: Prospective Cohort Study.

    abstract::Rationale: The overuse of antibiotics has been an important clinical issue, and antibiotic exposure is linked to alterations in gut microbiota, which has been related to risks of various chronic diseases such as cardiovascular disease and cancer. Also, duration of antibiotic exposure may be a risk factor of premature ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.119.315279

    authors: Heianza Y,Ma W,Li X,Cao Y,Chan AT,Rimm EB,Hu FB,Rexrode KM,Manson JE,Qi L

    更新日期:2020-01-31 00:00:00

  • Intimal injury and regrowth in the rabbit aorta; medial smooth muscle cells as a source of neointima.

    abstract::The present study was undertaken to determine the mechanism of neointima formation in rabbit arteries subjected to extensive endothelial desquamation. Endothelial cells were selectively removed from the abdominal aorta by passing an inflated balloon catheter through the vessel. The healing response was then studied se...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.36.1.58

    authors: Spaet TH,Stemerman MB,Veith FJ,Lejnieks I

    更新日期:1975-01-01 00:00:00

  • Endothelial cells of the human microvasculature express epidermal fatty acid-binding protein.

    abstract::Epidermal fatty acid-binding protein (E-FABP), previously characterized in human keratinocytes, is a cytoplasmic protein of 15 kD that specifically binds fatty acids (FAs). Previous PAGE-immunoblotting studies indicated that several human tissues display an immunoreactive band with an electrophoretic mobility identica...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.81.3.297

    authors: Masouyé I,Hagens G,Van Kuppevelt TH,Madsen P,Saurat JH,Veerkamp JH,Pepper MS,Siegenthaler G

    更新日期:1997-09-01 00:00:00

  • Extreme Acetylation of the Cardiac Mitochondrial Proteome Does Not Promote Heart Failure.

    abstract:RATIONALE:Circumstantial evidence links the development of heart failure to posttranslational modifications of mitochondrial proteins, including lysine acetylation (Kac). Nonetheless, direct evidence that Kac compromises mitochondrial performance remains sparse. OBJECTIVE:This study sought to explore the premise that ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.120.317293

    authors: Davidson MT,Grimsrud PA,Lai L,Draper JA,Fisher-Wellman KH,Narowski TM,Abraham DM,Koves TR,Kelly DP,Muoio DM

    更新日期:2020-09-25 00:00:00

  • Increased Epicardial Adipose Tissue Volume Correlates With Cardiac Sympathetic Denervation in Patients With Heart Failure.

    abstract:RATIONALE:It has been reported that epicardial adipose tissue (EAT) may affect myocardial autonomic function. OBJECTIVE:The aim of this study was to explore the relationship between EAT and cardiac sympathetic nerve activity in patients with heart failure. METHODS AND RESULTS:In 110 patients with systolic heart failu...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.115.307765

    authors: Parisi V,Rengo G,Perrone-Filardi P,Pagano G,Femminella GD,Paolillo S,Petraglia L,Gambino G,Caruso A,Grimaldi MG,Baldascino F,Nolano M,Elia A,Cannavo A,De Bellis A,Coscioni E,Pellegrino T,Cuocolo A,Ferrara N,Leosco D

    更新日期:2016-04-15 00:00:00

  • Mechanisms of Connexin-Related Lymphedema.

    abstract:RATIONALE:Mutations in GJC2 and GJA1, encoding Cxs (connexins) 47 and 43, respectively, are linked to lymphedema, but the underlying mechanisms are unknown. Because efficient lymph transport relies on the coordinated contractions of lymphatic muscle cells (LMCs) and their electrical coupling through Cxs, Cx-related lym...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.312576

    authors: Castorena-Gonzalez JA,Zawieja SD,Li M,Srinivasan RS,Simon AM,de Wit C,de la Torre R,Martinez-Lemus LA,Hennig GW,Davis MJ

    更新日期:2018-09-28 00:00:00

  • Gene expression in fibroblasts and fibrosis: involvement in cardiac hypertrophy.

    abstract::Structural remodeling of the ventricular wall is a key determinant of clinical outcome in heart disease. Such remodeling involves the production and destruction of extracellular matrix proteins, cell proliferation and migration, and apoptotic and necrotic cell death. Cardiac fibroblasts are crucially involved in these...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.res.0000046452.67724.b8

    authors: Manabe I,Shindo T,Nagai R

    更新日期:2002-12-13 00:00:00

  • Enhancement of potassium-sensitive current in heart cells by pinacidil. Evidence for modulation of the ATP-sensitive potassium channel.

    abstract::Pinacidil belongs to a novel group of compounds that enhance the potassium permeability of vascular smooth muscle. Evidence also exists that this drug enhances the potassium permeability of cardiac tissue. The purpose of the present investigation was to determine if pinacidil alters potassium-channel activity in heart...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.65.2.436

    authors: Arena JP,Kass RS

    更新日期:1989-08-01 00:00:00

  • Impairment in postischemic neovascularization in mice lacking the CXC chemokine receptor 3.

    abstract::Inflammatory cell infiltration is a feature of postischemic neovascularization. However, mechanisms leading to leukocyte attraction to the site of neovascularization are still undefined. We hypothesized that the CXC chemokine receptor 3 (CXCR3) may contribute to leukocyte accumulation and subsequently to blood vessel ...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.RES.0000159389.55544.20

    authors: Waeckel L,Mallat Z,Potteaux S,Combadière C,Clergue M,Duriez M,Bao L,Gerard C,Rollins BJ,Tedgui A,Levy BI,Silvestre JS

    更新日期:2005-03-18 00:00:00

  • Covalent and noncovalent modification of thin filament action: the essential role of troponin in cardiac muscle regulation.

    abstract::Troponin is essential for the regulation of cardiac contraction. Troponin is a sarcomeric molecular switch, directly regulating the contractile event in concert with intracellular calcium signals. Troponin isoform switching, missense mutations, proteolytic cleavage, and posttranslational modifications are known to dir...

    journal_title:Circulation research

    pub_type: 杂志文章,评审

    doi:10.1161/01.RES.0000110083.17024.60

    authors: Metzger JM,Westfall MV

    更新日期:2004-02-06 00:00:00

  • Contribution of vagal pathways to the renal responses to head-out immersion in the nonhuman primate.

    abstract::Studies were carried out to determine the contribution of cardiopulmonary receptors to the renal responses to head-out water immersion in the nonhuman primate. Immersion to the suprasternal notch was associated with significant increases in central venous pressure, urine flow, and sodium excretion. The increased sodiu...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/01.res.42.2.263

    authors: Gilmore JP,Zucker IH

    更新日期:1978-02-01 00:00:00

  • Receptor-Mediated Mechanism Controlling Tissue Levels of Bioactive Lipid Oxidation Products.

    abstract:RATIONALE:Oxidative stress is an important contributing factor in several human pathologies ranging from atherosclerosis to cancer progression; however, the mechanisms underlying tissue protection from oxidation products are poorly understood. Oxidation of membrane phospholipids, containing the polyunsaturated fatty ac...

    journal_title:Circulation research

    pub_type: 杂志文章

    doi:10.1161/CIRCRESAHA.117.305925

    authors: Kim YW,Yakubenko VP,West XZ,Gugiu GB,Renganathan K,Biswas S,Gao D,Crabb JW,Salomon RG,Podrez EA,Byzova TV

    更新日期:2015-07-31 00:00:00