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 inhibitor protein, called beta-arrestin. Two isoforms have been identified both for beta ARK and for beta-arrestin. In the present study, we have investigated the expression of the individual isoforms of beta-arrestin and of beta ARK in left ventricles from failing and control human hearts. mRNAs for all four proteins, beta-arrestin-1, beta-arrestin-2, beta ARK-1, and beta ARK-2, were identified in human heart. Quantitation by reverse-transcription polymerase chain reactions showed that in heart failure there were no changes of the mRNA levels for beta-arrestin-1 and beta-arrestin-2, a slight (< 50%) increase of the mRNA for beta ARK-2, and a threefold increase for beta ARK-1 mRNA. At the protein level, beta-arrestin-1 was readily detected by Western blotting in human heart. Its absolute values were approximately 350 fmol/mg cytosolic protein, and its expression was not changed in heart failure. beta-Arrestin-2 levels were too low to be detectable using the same methods. beta ARK levels as determined by enzymatic activity were approximately 20 fmol/mg cytosolic protein (beta ARK-1 plus beta ARK-2) and thus almost 20-fold lower than those of beta-arrestin. beta ARK levels were increased approximately twofold in heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)
journal_name
Circ Resjournal_title
Circulation researchauthors
Ungerer M,Parruti G,Böhm M,Puzicha M,DeBlasi A,Erdmann E,Lohse MJdoi
10.1161/01.res.74.2.206subject
Has Abstractpub_date
1994-02-01 00:00:00pages
206-13issue
2eissn
0009-7330issn
1524-4571journal_volume
74pub_type
杂志文章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::Stimulation of beta-adrenergic receptors (betaARs) causes apoptosis in adult rat ventricular myocytes (ARVMs). The role of reactive oxygen species (ROS) in mediating betaAR-stimulated apoptosis is not known. Stimulation of betaARs with norepinephrine (10 micromol/L) in the presence of prazosin (100 nmol/L) for 24 hour...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000054624.03539.b4
更新日期:2003-02-07 00:00:00
abstract::Nonischemic dilated cardiomyopathy (DCM) often has a genetic pathogenesis. Because of the large number of genes and alleles attributed to DCM, comprehensive genetic testing encompasses ever-increasing gene panels. Genetic diagnosis can help predict prognosis, especially with regard to arrhythmia risk for certain subty...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.309396
更新日期:2017-09-15 00:00:00
abstract::Alpha1-adrenoceptor (alpha1-AR) stimulation increases sarcolemmal Na+-H+ exchanger (NHE) activity. The present study was designed to determine the role(s) of alpha1-AR subtype(s) in mediating this response. As an index of NHE activity, acid efflux rates (JHs) were determined in single rat ventricular myocytes loaded w...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.10.1078
更新日期:1998-06-01 00:00:00
abstract::Adenosine modulates a variety of cellular functions by interacting with specific cell surface G protein-coupled receptors (A1, A2A, A2B, and A3) and is a potential mediator of angiogenesis through the A2B receptor. The lack of a potent, selective A2B receptor inhibitor has hampered its characterization. Our goal was t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000091260.78959.BC
更新日期:2003-09-19 00:00:00
abstract::Increased glomerular capillary hydrostatic pressure (PGC) is an important hemodynamic determinant of glomerular injury, but the molecular events responsible for this association are poorly understood. PGC is normal in spontaneously hypertensive rats (SHR), but uninephrectomy leads to an increase in PGC and accelerated...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.5.844
更新日期:1994-11-01 00:00:00
abstract::Patients with severe heart failure are at high risk of sudden cardiac death. In the majority of these patients, sudden cardiac death is thought to be due to ventricular tachyarrhythmias. Alterations of the electric properties of single myocytes in heart failure may favor the occurrence of ventricular arrhythmias in th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.11.1206
更新日期:1998-06-15 00:00:00
abstract:RATIONALE:Allogeneic mesenchymal precursor cells (MPCs) have been effective in large animal models of ischemic and nonischemic heart failure (HF). OBJECTIVE:To evaluate the feasibility and safety of 3 doses (25, 75, or 150 million cells) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial. MET...
journal_title:Circulation research
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCRESAHA.115.306332
更新日期:2015-08-28 00:00:00
abstract::Increasing attention is currently devoted to the multiple roles that pericytes (also defined as mural, Rouget, or perivascular cells) may play during angiogenesis, vascular homeostasis, and pathology. Many recent excellent reviews thoroughly address these topics (see below); hence, we will not discuss them in detail h...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300203
更新日期:2013-07-19 00:00:00
abstract::The present series of experiments used gas chromatography to identify vapor-phase photoproducts liberated during excimer laser irradiation of cardiovascular tissues in air and blood. In air, laser beams produced from ArF (193 nm) and XeF (351 nm) excimer laser gas mixtures were delivered to samples of myocardium and a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.3.429
更新日期:1987-03-01 00:00:00
abstract:RATIONALE:Hypoxia promotes renal damage and progression of chronic kidney disease (CKD). The erythrocyte is the only cell type for oxygen (O2) delivery. Sphingosine 1-phosphate (S1P)-a highly enriched biolipid in erythrocytes-is recently reported to be induced under high altitude in normal humans to enhance O2 delivery...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.316298
更新日期:2020-07-17 00:00:00
abstract::Despite improvements in the therapy of underlying heart disease, sudden cardiac death is a major cause of death worldwide. Disturbed Na and Ca handling is known to be a major predisposing factor for life-threatening tachyarrhythmias. In cardiomyocytes, many ion channels and transporters, including voltage-gated Na and...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.304678
更新日期:2015-06-05 00:00:00
abstract::A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase ac...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.8
更新日期:1975-01-01 00:00:00
abstract::The goal of this study was to test the hypothesis that the cardioprotective effects of the late phase of ischemic preconditioning (PC) can be mimicked by treatment with NO donors. In phase I (studies of myocardial stunning), conscious rabbits underwent a sequence of six 4-minute coronary occlusion/4-minute reperfusion...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.1.73
更新日期:1998-07-13 00:00:00
abstract::Our objective was to test the hypotheses that 1) myoplasmic [Ca2+] is the primary determinant of crossbridge phosphorylation and that 2) phosphorylation is the primary determinant of crossbridge interactions with the thin filament in swine carotid arterial smooth muscle. We tested these hypotheses by evaluating the re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.3.593
更新日期:1988-09-01 00:00:00
abstract:RATIONALE:Cardiac myocyte-specific deletion of either glycogen synthase kinase (GSK)-3α and GSK-3β leads to cardiac protection after myocardial infarction, suggesting that deletion of both isoforms may provide synergistic protection. This is an important consideration because of the fact that all GSK-3-targeted drugs, ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308544
更新日期:2016-04-15 00:00:00
abstract:RATIONALE:Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315506
更新日期:2020-01-03 00:00:00
abstract::We investigated the effects of streptozotocin-induced diabetes on atrial natriuretic peptide (ANP) synthesis, hemodynamic parameters, blood volume, and histopathology, as well as the reversibility of such effects with insulin therapy in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs). The biatrial A...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.4.803
更新日期:1990-10-01 00:00:00
abstract::Endocardial endothelium and endothelium of coronary vessels produce NO. Histochemical methods have suggested that coronary arterial endothelial cells contain more endothelial constitutive NO synthase (ecNOS) than does coronary venous endothelium. We have further investigated the distribution of ecNOS in cardiac endoth...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.82.2.195
更新日期:1998-02-09 00:00:00
abstract::The effects of Bay K 8644 on the high-threshold calcium channel was investigated by means of the whole-cell patch-clamp technique in single guinea pig ventricular myocytes. The goal of the experiments was to characterize the inhibitory effects of Bay K 8644 on the calcium channel, and identify the factors that influen...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.1.97
更新日期:1988-01-01 00:00:00
abstract:RATIONALE:A hallmark of chronic inflammatory disorders is persistence of proinflammatory macrophages in diseased tissues. In atherosclerosis, this is associated with dyslipidemia and oxidative stress, but mechanisms linking these phenomena to macrophage activation remain incompletely understood. OBJECTIVE:To investiga...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.119.315833
更新日期:2019-12-06 00:00:00
abstract:RATIONALE:Transcatheter, intramyocardial injections of bone marrow-derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. OBJECTIVE:We used cardiac MRI (CMR) in patients with left ventricular (LV) dysfunction related to remote myocardial infarction (MI) to test the hypothes...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.242610
更新日期:2011-04-01 00:00:00
abstract::Adipose tissue (AT) can accumulate macrophages and secrete several inflammatory mediators. Despite its pivotal role in the progression of chronic inflammatory processes such as atherosclerosis, the adaptive role of immunity in obesity remains poorly explored. Visceral AT of diet-induced obese C57BL/6 mice had higher n...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.108.177105
更新日期:2008-08-29 00:00:00
abstract::Although vascular endothelial growth factor (VEGF) has been described as a potent angiogenic stimulus, its application in therapy remains difficult: blood vessels formed by exposure to VEGF tend to be malformed and leaky. In nature, the principal form of VEGF possesses a binding site for ECM components that maintain i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000126411.29641.08
更新日期:2004-04-30 00:00:00
abstract::RhoA and Rac1 regulate formation of stress fibers and intercellular junctions, thus modulating endothelial monolayer permeability. Posttranslational modifications of RhoA and Rac1 regulate enzyme activity and subcellular localization, resulting in altered cellular function. The role of RhoA and Rac1 carboxyl methylati...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000113923.85084.C1
更新日期:2004-02-20 00:00:00
abstract:RATIONALE:The high morbidity/mortality of atherosclerosis is typically precipitated by plaque rupture and consequent thrombosis. However, research on underlying mechanisms and therapeutic approaches is limited by the lack of animal models that reproduce plaque instability observed in humans. OBJECTIVE:Development and ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301562
更新日期:2013-07-19 00:00:00
abstract::The molecular identity of receptor-operated, nonselective cation channels (ROCs) of vascular smooth muscle (VSM) cells is not known for certain. Mammalian homologues of the Drosophila canonical transient receptor potential channels (TRPCs) are possible candidates. This study tested the hypothesis that heteromultimeric...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000226495.34949.28
更新日期:2006-06-23 00:00:00
abstract::Available data demonstrate that oxygen free radicals and derived reactive species of oxygen are produced during myocardial ischemia as well as upon reperfusion of the ischemic tissue. The present study was designed to determine if polyethylene glycol-conjugated superoxide dismutase (PEG-SOD), with its extended plasma ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.4.665
更新日期:1989-04-01 00:00:00
abstract:RATIONALE:Wnt signaling regulates key aspects of diabetic vascular disease. OBJECTIVE:We generated SM22-Cre;LRP6(fl/fl);LDLR(-/-) mice to determine contributions of Wnt coreceptor low-density lipoprotein receptor-related protein 6 (LRP6) in the vascular smooth muscle lineage of male low-density lipoprotein receptor-nu...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.117.306712
更新日期:2015-07-03 00:00:00
abstract::A period of prolonged vasodilation follows flow-restricted exercise of skeletal muscle. We tested the hypothesis that adenosine participates in mediating this vascular response. Vascularly isolated, anterior calf muscles of anesthetized dogs were stimulated to contract at a rate of 4 twitches/sec. Blood flow was held ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.6.759
更新日期:1979-06-01 00:00:00