Abstract:
:The regulation of mitogen-activated protein kinase (MAPK) and MAPK kinase (MEK) was studied in freshly isolated adult rat heart preparations. In contrast to the situation in ventricular myocytes cultured from neonatal rat hearts, stimulation of MAPK activity by 1 mumol/L phorbol 12-myristate 13-acetate (PMA) was not consistently detectable in crude extracts. After fast protein liquid chromatography, MAPK isoforms p42MAPK and p44MAPK and two peaks of MEK were shown to be activated > 10-fold in perfused hearts or ventricular myocytes exposed to 1 mumol/L PMA for 5 minutes. The identities of MAPK or MEK were confirmed by immunoblotting and, for MAPK, by the "in-gel" myelin basic protein phosphorylation assay. In retrogradely perfused hearts, high coronary perfusion pressure (120 mm Hg for 5 minutes), norepinephrine (50 mumol/L for 5 minutes), or isoproterenol (50 mumol/L for 5 minutes) stimulated MAPK and MEK approximately 2- to 5-fold. In isolated myocytes, endothelin 1 (100 nmol/L for 5 minutes) also stimulated MAPK, but stimulation by norepinephrine or isoproterenol was difficult to detect. Immunoblotting showed that the relative abundances of MAPK and MEK protein in ventricles declined to < 20% of their postpartal abundances after 50 days. This may explain the difficulties encountered in assaying the activity of MAPK in crude extracts from adult hearts. We conclude that potentially hypertrophic agonists and interventions stimulate the MAPK cascade in adult rats and suggest that the MAPK cascade may be an important intracellular signaling pathway in this response.
journal_name
Circ Resjournal_title
Circulation researchauthors
Lazou A,Bogoyevitch MA,Clerk A,Fuller SJ,Marshall C J,Sugden PHdoi
10.1161/01.res.75.5.932subject
Has Abstractpub_date
1994-11-01 00:00:00pages
932-41issue
5eissn
0009-7330issn
1524-4571journal_volume
75pub_type
杂志文章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
更新日期:1988-02-01 00:00:00
abstract:RATIONALE:Studies have demonstrated that exosomes can repair cardiac tissue post-myocardial infarction and recapitulate the benefits of cellular therapy. OBJECTIVE:We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)-derived exosomes in a rat model of ischemia-reperfusion inj...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.309935
更新日期:2017-02-17 00:00:00
abstract::Patients with peripheral artery disease (PAD) are at heightened risk of both systemic cardiovascular adverse events, as well as limb-related morbidity. The optimal management of patients with PAD requires a comprehensive treatment strategy incorporating both lifestyle changes, including smoking cessation and exercise,...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.114.303505
更新日期:2015-04-24 00:00:00
abstract::We determined age-related differences in automaticity and responsiveness of cardiac Purkinje fibers from adult and neonatal dogs to graded concentrations of epinephrine, isoproterenol, and phenylephrine. Purkinje fibers were studied with standard microelectrode techniques during superfusion with Tyrode's solution at 3...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.40.4.390
更新日期:1977-04-01 00:00:00
abstract:RATIONALE:Smooth muscle precursor cells have previously been reported to reside in bone marrow and in the circulation, but little is currently known regarding the proximate stimuli for smooth muscle cell differentiation of these putative progenitors. OBJECTIVE:Because local thrombin generation occurs as an initial res...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.199984
更新日期:2009-07-31 00:00:00
abstract::Our goal in this review is to discuss the pathophysiology, diagnosis, and treatment of stroke caused by atherosclerosis of the major intracranial arteries. References for the review were identified by searching PubMed for related studies published from 1955 to June 2016 using search terms intracranial stenosis and int...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.308441
更新日期:2017-02-03 00:00:00
abstract:RATIONALE:Yes-associated protein (YAP), the terminal effector of the Hippo signaling pathway, is crucial for regulating embryonic cardiomyocyte proliferation. OBJECTIVE:We hypothesized that YAP activation after myocardial infarction (MI) would preserve cardiac function and improve survival. METHODS AND RESULTS:We use...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.303632
更新日期:2014-07-18 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: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::After myocardial infarction (MI), the noninfarcted myocardium undergoes significant hypertrophy as part of the post-MI structural remodeling. Electrophysiological changes associated with the hypertrophied remodeled myocardium may play a key role in arrhythmia generation in the post-MI heart. We investigated the cellul...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.3.461
更新日期:1996-09-01 00:00:00
abstract::The arterial pressure of rabbits with chronic one-kidney hypertension can be lowered to normotensive levels by direct immunization with preparations made from the cortex of hog kidneys. Hypertensive rabbits that are immunized with large amounts of renin may develop high plasma antirenin titers without affecting their ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.3.400
更新日期:1976-09-01 00:00:00
abstract::Studies of the stellate ganglion and middle cervical ganglion indicate that sympathetic efferent nerve activity can be modified by peripheral excitatory inputs and that these neural connections may function as pathways for a peripheral reflex at the level of the thoracic sympathetic ganglia. This excitatory synaptic i...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.3.554
更新日期:1989-03-01 00:00:00
abstract::Smooth muscle expresses the Ialpha and the Ibeta isoforms of cGMP-dependent protein kinase I (cGKI). Inactivation of the murine cGKI gene prkg1 leads to multiple phenotypes and premature death at approximately 6 weeks. We reconstituted mice with the cGKIalpha or -Ibeta isozyme to test which isozyme was needed to suppo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.154351
更新日期:2007-11-26 00:00:00
abstract::Confocal imaging was used to study the influence of cytosolic ATP on the properties of spontaneous Ca(2+) sparks in permeabilized ventricular myocytes. Cells were perfused with mock intracellular solutions containing fluo 3. Reducing [ATP] to <0.5 mmol/L decreased the frequency but increased the amplitude of spontaneo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1801.096264
更新日期:2001-09-14 00:00:00
abstract::Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiograph...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000016960.61087.86
更新日期:2002-05-03 00:00:00
abstract::To investigate the dynamic control of cardiac ATP synthesis, we simultaneously determined the time course of mitochondrial oxygen consumption with the time course of changes in high-energy phosphates following steps in cardiac energy demand. Isolated isovolumically contracting rabbit hearts were perfused with Tyrode's...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.4.751
更新日期:1994-10-01 00:00:00
abstract:RATIONALE:Giant-cell arteritis (GCA) is a large-vessel vasculitis characterized by immune cell infiltration, yet the potential involvement of neutrophils has rarely been studied. OBJECTIVE:We investigated whether alterations in neutrophil reactivity occurred in the pathogenesis of GCA or during its clinical management...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.301374
更新日期:2014-01-17 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::Heme oxygenase (HO) is a cytoprotective enzyme that degrades heme (a potent oxidant) to generate carbon monoxide (a vasodilatory gas that has anti-inflammatory properties), bilirubin (an antioxidant derived from biliverdin), and iron (sequestered by ferritin). Because of properties of HO and its products, we hypothesi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1001.091521
更新日期:2001-05-25 00:00:00
abstract::Hypertrophic (HCM) and dilated (DCM) cardiomyopathies are inherited diseases with a high incidence of death due to electric abnormalities or outflow tract obstruction. In many of the families afflicted with either disease, causative mutations have been identified in various sarcomeric proteins. In this review, we focu...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.110.223842
更新日期:2012-07-20 00:00:00
abstract::Cardiac allograft vasculopathy (CAV) continues to be a major cause of late graft failure after cardiac transplantation. We have demonstrated that Rho-kinase, an effector of the small GTPase Rho, plays an important role in the pathogenesis of arteriosclerosis. In this study, we examined whether the Rho-kinase-mediated ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000107196.21335.2B
更新日期:2004-01-09 00:00:00
abstract::Electrical field stimulation (EFS) of phenylephrine-contracted bovine mesenteric arteries pretreated with guanethidine elicited a relaxation that amounted to roughly 40%. This relaxation was sensitive to tetrodotoxin pretreatment, suggesting a neurogenic origin. The EFS-induced relaxation was correlated to an increase...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.3.756
更新日期:1991-03-01 00:00:00
abstract::Complete knowledge of myocardial structure, metabolism, and function is crucial to understanding the response of the heart to injury such as ischemia. Increasingly, this type of knowledge is required at multiple levels, from that of the isolated myocyte to the functioning organism, to provide basic scientists and clin...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000103863.40055.E8
更新日期:2003-12-12 00:00:00
abstract:RATIONALE:We have recently shown that the bone morphogenetic protein (BMP) antagonist Gremlin 2 (Grem2) is required for early cardiac development and cardiomyocyte differentiation. Our initial studies discovered that Grem2 is strongly induced in the adult heart after experimental myocardial infarction (MI). However, th...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.116.308700
更新日期:2016-07-22 00:00:00
abstract::Although Ca(2+) waves in cardiac myocytes are regarded as arrhythmogenic substrates, their properties in the heart in situ are poorly understood. On the hypothesis that Ca(2+) waves in the heart behave diversely and some of them influence the cardiac function, we analyzed their incidence, propagation velocity, and int...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.10.1093
更新日期:2000-05-26 00:00:00
abstract::Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed in...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.39.6.772
更新日期:1976-12-01 00:00:00
abstract::The influence of endothelin 1 on intracellular Ca2+ transients and isometric contractions was investigated in ferret papillary muscles loaded with the Ca(2+)-regulated bioluminescent indicator aequorin. In concentrations of 3 x 10(-9) to 1 x 10(-7) M, endothelin produced dose-dependent increases in the amplitudes of b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.3.582
更新日期:1991-09-01 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
abstract::We have cloned from cultured vascular smooth muscle cells a protein tyrosine phosphatase, rat density-enhanced phosphatase-1 (rDEP-1), which is a probable rat homologue of DEP-1/HPTP eta. rDEP-1 is encoded by an 8.7-kb transcript and is expressed as a 180- to 220-kD protein. The rDEP-1 gene is located on human chromos...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.3.570
更新日期:1996-09-01 00:00:00
abstract::Ablation of the enzyme phosphoinositide 3-kinase (PI3K)gamma (PI3Kgamma(-/-)) in mice increases cardiac contractility by elevating intracellular cAMP and enhancing sarcoplasmic reticulum Ca(2+) handling. Because cAMP is a critical determinant of heart rate, we investigated whether heart rate is altered in mice lacking...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.158428
更新日期:2007-12-07 00:00:00