Abstract:
:The structure-function relationships of the sarcomeric proteins in the mammalian cardiac compartment remain ill-defined because of the lack of a suitable model in which they can be readily manipulated or exchanged in vivo. To establish the validity of the transgenic paradigm for remodeling the mammalian heart, the murine alpha -cardiac myosin heavy chain gene promoter was used to express a ventricular myosin light chain-2 transgene (MLC2v) in both the atria and ventricles of the adult animal. Expression resulted in high levels of the transgene's transcript in both compartments. In the ventricle, the transgene was expressed against the background expression of the normal isoform. In the atrium, the transgene's expression would be ectopic, in that normally, MLC2v expression is restricted to the ventricle. Ectopic expression of the transgene in the atria resulted in a complete replacement of the atrial myosin light chain-2 protein isoform, although the endogenous isoform's steady state transcript levels were unchanged. In contrast, ventricular expression of the transgene had no effect at the protein level, despite an eightfold increase in MLC2v transcript levels. The data show that sarcomeric protein stoichiometry is maintained rigorously via posttransciptional regulation and that protein replacement can be achieved through a single transgenic manipulation.
journal_name
Circ Resjournal_title
Circulation researchauthors
Palermo J,Gulick J,Colbert M,Fewell J,Robbins Jdoi
10.1161/01.res.78.3.504subject
Has Abstractpub_date
1996-03-01 00:00:00pages
504-9issue
3eissn
0009-7330issn
1524-4571journal_volume
78pub_type
杂志文章abstract::To determine the time course of efferent sympathetic denervation after transmural myocardial infarction (TMI) and of efferent vagal denervation after transmural or nontransmural myocardial infarction (NTMI), we measured effective refractory periods (ERP) basal and apical to TMI or NTMI in secobarbital-anesthetized, op...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.6.1111
更新日期:1988-06-01 00:00:00
abstract::We hypothesized that both acute and chronic accumulation of myocardial interstitial edema (extravascular fluid [EVF]) would compromise cardiac function. We also postulated that excess fluid within the myocardial interstitial space would potentiate interstitial fibrosis, thus further compromising function. Dogs were di...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.6.1713
更新日期:1991-06-01 00:00:00
abstract::Osteopontin (OPN) is a multifunctional cytokine that is strongly expressed in healing wounds and fibrotic lesions, both of which are characterized by the formation of myofibroblasts. We examined the role of OPN in myofibroblast differentiation induced by the profibrotic cytokine transforming growth factor-beta1. In cu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.160408
更新日期:2008-02-15 00:00:00
abstract:RATIONALE:The cardiac inwardly rectifying K(+) current (I(K1)) plays a critical role in modulating excitability by setting the resting membrane potential and shaping phase 3 of the cardiac action potential. OBJECTIVE:This study aims to analyze the effects of nitric oxide (NO) on human atrial I(K1) and on Kir2.1 channe...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.197558
更新日期:2009-08-14 00:00:00
abstract::Catecholamines have been implicated in the phenomenon of ischemic preconditioning. We have previously demonstrated that ischemic preconditioning against postischemic mechanical dysfunction in the isolated rat heart is mediated by the alpha 1-adrenergic receptor. The purpose of this study was to delineate the signal tr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.1.73
更新日期:1995-01-01 00:00:00
abstract::The aim of the study was to investigate whether the adrenal renin-angiotensin system plays an independent role in the regulation of mineralocorticoid biosynthesis in the adrenal gland and to explore the mechanisms of this action. Twelve-week-old male Sprague-Dawley rats were studied: 22 rats were maintained on a regul...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.5.857
更新日期:1997-11-01 00:00:00
abstract::Fractalkine, a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1, and the CX3CR1 polymorphism V249I affects receptor expression and function. Here we show that this polymorphism is an independent risk factor for atherosclerotic coronary artery disease (CAD). ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1701.095642
更新日期:2001-08-31 00:00:00
abstract::Previous work has shown that neutrophils isolated from whole blood adhere to cardiac-myocytes via CD18 (beta 2 integrin) to cause injury to the heart cells. In vitro, we have found that upon endothelial transmigration, neutrophils can also express alpha 4 beta 1; however, whether this contributes to neutrophil adhesio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.2.196
更新日期:1997-08-01 00:00:00
abstract::In the present study, we investigated the modulatory role of the epicardium in myocardial and coronary development. Epicardial cell tracing experiments have shown that epicardium-derived cells are the source of interstitial myocardial fibroblasts, cushion mesenchyme, and smooth muscle cells. Epicardial outgrowth inhib...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.11.969
更新日期:2000-11-24 00:00:00
abstract:RATIONALE:Elevations in C-reactive protein (CRP) are associated with increased cardiovascular disease risk and endothelial dysfunction. CRP antagonizes endothelial nitric oxide synthase (eNOS) through processes mediated by the IgG receptor Fcγ receptor IIB (FcγRIIB), its immunoreceptor tyrosine-based inhibitory motif, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.254573
更新日期:2011-10-28 00:00:00
abstract::To see how serotonin affects filtration from lung vessels, we measured vascular pressures, lung lymph flow, lung lymph and blood plasma protein concentrations, arterial blood gases, cardiac output, and lung water content in unanesthetized sheep before and during intravenous serotonin infusions and compared serotonin e...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.761
更新日期:1975-06-01 00:00:00
abstract:RATIONALE:Protein kinase (PK)C-induced phosphorylation of cardiac troponin (cTn)I has been shown to regulate cardiac contraction. OBJECTIVE:Characterize functional effects of increased PKC-induced cTnI phosphorylation and identify underlying mechanisms using a transgenic mouse model (cTnI(PKC-P)) expressing mutant cTn...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.205427
更新日期:2009-12-04 00:00:00
abstract::The beta-adrenergic receptor system of the failing human heart is markedly desensitized. We have recently postulated that this desensitization may in part be caused by an increase in beta-adrenergic receptor kinase (beta ARK) expression. beta ARK is thought to effect desensitization by acting in concert with an inhibi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.74.2.206
更新日期:1994-02-01 00:00:00
abstract::Canine cardiac Purkinje cells contain both L- and T-type calcium currents, yet the single Ca2+ channels have not been characterized from these cells. Additionally, previous studies have shown an overlap between the steady-state inactivation and activations curves for L-type Ca2+ currents, suggesting the presence of L-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.3.456
更新日期:1992-03-01 00:00:00
abstract::An increase in plasma renin activity was demonstrated in plasma from normal subjects and most patients with essential hypertension after prolonged storage of the plasma at -20 degrees C. No change in renin substrate concentration was observed after storage for 12 months, and the rate of angiotensin generation during i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.6.10
更新日期:1975-06-01 00:00:00
abstract:RATIONALE:Chronic rejection, accelerated coronary atherosclerosis, myocardial infarction, and ischemic heart failure determine the unfavorable evolution of the transplanted heart in humans. OBJECTIVE:Here we tested whether the pathological manifestations of the transplanted heart can be corrected partly by a strategy ...
journal_title:Circulation research
pub_type: 杂志文章,收录出版
doi:10.1161/CIRCRESAHA.109.207266
更新日期:2009-11-20 00:00:00
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
更新日期:2009-07-17 00:00:00
abstract::Increasing evidence suggests that endogenous NO inhibits sympathetic outflow in anesthetized animals. However, in a recent study from this laboratory, we were unable to find any evidence of increased renal sympathetic nerve activity (RSNA) in response to blockade of NO synthesis in conscious rabbits. Because angiotens...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.4.496
更新日期:1998-03-09 00:00:00
abstract::Apolipoprotein E-deficient (ApoE-/-) mice develop atherosclerotic lesions throughout the arterial tree, including the carotid bifurcation. Although the expression of adhesion molecules such as ICAM-1, vascular cell adhesion molecule-1 (VCAM-1), and P-selectin on endothelium that overlie atherosclerotic plaques has bee...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.11.1237
更新日期:1999-06-11 00:00:00
abstract::Caspase-1 processes the interleukin (IL)-1beta and IL-18 inactive precursors to the biologically active cytokines that are known to have proatherogenic effects. The present study investigated the genetic variability of the CASP1 gene and plasma levels of caspase-1 in relation to cardiovascular risk. In Europeans, 3 ta...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000232324.87983.4b
更新日期:2006-07-07 00:00:00
abstract::An improved assay was used to investigate the effects of hypoxia or ischemia on interstitial fluid and coronary venous effluent levels of adenosine in isolated perfused nonworking rat hearts. The adenosine in 5- to 10-microliter samples of left ventricular epicardial surface transudates and coronary effluents was reac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.2.177
更新日期:1987-02-01 00:00:00
abstract:RATIONALE:B-1 cell-derived natural IgM antibodies against oxidation-specific epitopes on low-density lipoprotein are anti-inflammatory and atheroprotective. Bone marrow (BM) B-1a cells contribute abundantly to IgM production, yet the unique repertoire of IgM antibodies generated by BM B-1a and the factors maintaining t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315786
更新日期:2019-10-25 00:00:00
abstract:RATIONALE:The vascular adventitia is a complex layer of the vessel wall consisting of vasa vasorum microvessels, nerves, fibroblasts, immune cells, and resident progenitor cells. Adventitial progenitors express the stem cell markers, Sca1 and CD34 (adventitial sca1-positive progenitor cells [AdvSca1]), have the potenti...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.309322
更新日期:2017-01-20 00:00:00
abstract::Beta(1)- and beta(2)-adrenergic receptors (betaARs) are known to differentially regulate cardiomyocyte contraction and growth. We tested the hypothesis that these differences are attributable to spatial compartmentation of the second messenger cAMP. Using a fluorescent resonance energy transfer (FRET)-based approach, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000250046.69918.d5
更新日期:2006-11-10 00:00:00
abstract::Pacemaker and conduction system myocytes play crucial roles in initiating and regulating the contraction of the cardiac chambers. Genetic defects, acquired diseases, and aging cause dysfunction of the pacemaker and conduction tissues, emphasizing the clinical necessity to understand the molecular and cellular mechanis...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.109.205419
更新日期:2010-02-05 00:00:00
abstract::Angiotensin II and its metabolites, [des-Asp-1]-angiotensin II (angiotensin III), [des-(Asp-1,Arg-2)]angiotensin II, and [des-(Asp-1,Arg-2,val-3)]angiotensin II, were measured in arterial and venous plasma from normal rats. Paper chromatography was used to separate the peptides which were measured with a radioimmunoas...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.38.6.122
更新日期:1976-06-01 00:00:00
abstract::14-3-3 family members are dimeric phosphoserine-binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Targeted expression of dominant-negative 14-3-3eta (DN-14-3-3) to murine postnatal cardiac tissue potentiates Ask1, c-jun N-terminal kinase (JNK), and p38 mitogen-activated pr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000104084.88317.91
更新日期:2003-11-28 00:00:00
abstract::Pharmacological modulation of [K+]o accumulation and action potential changes during acute myocardial ischemia is under evaluation as a promising new antiarrhythmic and cardioprotective strategy during myocardial ischemia and reperfusion. We studied the effects of cromakalim, a K+ channel opener that activates ATP-sen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.6.1324
更新日期:1992-12-01 00:00:00
abstract::A variety of delivery systems have been used to genetically modify vascular endothelial cells and smooth muscle cells (SMCs), but currently available systems suffer from either inefficient in vivo gene transfer, transient episomal vector expression, or significant immune responses and inflammation. In the present stud...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::We studied postclamp renal artery pressure and renin release in eight conscious dogs with one-kidney Goldblatt hypertension. On normal sodium intake, intrarenal blockade of angiotensin II with Sar1-Ala8-angiotension II (P-113, saralasin acetate) markedly decreased postclamp renal artery pressure and increased renin re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.3.238
更新日期:1977-03-01 00:00:00