Abstract:
RATIONALE:Mechanisms underlying diastolic dysfunction need to be better understood. OBJECTIVE:To study the role of titin in diastolic dysfunction using a mouse model of experimental heart failure induced by transverse aortic constriction. METHODS AND RESULTS:Eight weeks after transverse aortic constriction surgery, mice were divided into heart failure (HF) and congestive heart failure (CHF) groups. Mechanical studies on skinned left ventricle myocardium measured total and titin-based and extracellular matrix-based passive stiffness. Total passive stiffness was increased in both HF and CHF mice, and this was attributable to increases in both extracellular matrix-based and titin-based passive stiffness, with titin being dominant. Protein expression and titin exon microarray analysis revealed increased expression of the more compliant N2BA isoform at the expense of the stiff N2B isoform in HF and CHF mice. These changes are predicted to lower titin-based stiffness. Because the stiffness of titin is also sensitive to titin phosphorylation by protein kinase A and protein kinase C, back phosphorylation and Western blot assays with novel phospho-specific antibodies were performed. HF and CHF mice showed hyperphosphorylation of protein kinase A sites and the proline glutamate valine lysine (PEVK) S26 protein kinase C sites, but hypophosphorylation of the PEVK S170 protein kinase C site. Protein phosphatase I abolished differences in phosphorylation levels and normalized titin-based passive stiffness levels between control and HF myocardium. CONCLUSION:Transverse aortic constriction-induced HF results in increased extracellular matrix-based and titin-based passive stiffness. Changes in titin splicing occur, which lower passive stiffness, but this effect is offset by hyperphosphorylation of residues in titin spring elements, particularly of PEVK S26. Thus, complex changes in titin occur that combined are a major factor in the increased passive myocardial stiffness in HF.
journal_name
Circ Resjournal_title
Circulation researchauthors
Hudson B,Hidalgo C,Saripalli C,Granzier Hdoi
10.1161/CIRCRESAHA.111.246819subject
Has Abstractpub_date
2011-09-30 00:00:00pages
858-66issue
8eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.111.246819journal_volume
109pub_type
杂志文章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::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:RATIONALE:Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported. OBJECTIVE:Explore whether serum beta carotene is associated with overall and cause-specific ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313409
更新日期:2018-12-07 00:00:00
abstract::The effects of sodium pump inhibition produced by exposure to the cardiac glycosides, ouabain or dihydroouabain, or by reduction in extracellular potassium to 1.0 mM, on contractile state and sodium-calcium exchange were studied in primary monolayer cultures of chick embryo ventricular cells. Ouabain, 10(-6)M, dihydro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.56.2.231
更新日期:1985-02-01 00:00:00
abstract::Contraction and relaxation of vascular smooth muscle and cardiac myocytes are key physiological events in the cardiovascular system. These events are regulated by second messengers, cAMP and cGMP, in response to extracellular stimulants. The strength of signal transduction is controlled by intracellular cyclic nucleot...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000256354.95791.f1
更新日期:2007-02-16 00:00:00
abstract::The aging population is increasing in developed countries. Because the incidence of cardiac disease increases dramatically with age, it is important to understand the molecular mechanisms through which the heart becomes either more or less susceptible to stress. Cardiac aging is characterized by the presence of hypert...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.307474
更新日期:2016-05-13 00:00:00
abstract::When exposed to an increasing transmural pressure, middle cerebral arteries of the cat exhibit reduction of internal diameter which is mediated by vascular muscle cell depolarization. This laboratory has recently demonstrated that this "pressure-induced" activation is dependent upon the presence of an intact endotheli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.193
更新日期:1989-07-01 00:00:00
abstract::The purpose of this study was to determine the coronary microvascular sites of autoregulation. The epimyocardial coronary microcirculation was observed through an intravital microscope by stroboscopic epi-illumination in anesthetized open-chest dogs (n = 20). Aortic pressure and heart rate were held constant by an aor...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.2.389
更新日期:1990-02-01 00:00:00
abstract::The pulmonary vein is sleeved by myocardium, which is a major source of atrial fibrillation and is involved in congenital sinus venosus defects. Little is known about the cellular origin and mechanism of formation of the pulmonary myocardium. We observed a biphasic process of pulmonary myocardium formation in mice. Fi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.161182
更新日期:2007-10-26 00:00:00
abstract::The influence of inhibition of the Na+ pump, with secondary stimulation of Na+-Ca++ exchange, on cellular Ca++ distribution is examined using the on-line scintillation disk technique and cultured neonatal rat myocardial cells. Under control conditions, La+++ displaced 78.1 +/- 1.13% (SEM) of the total cell associated ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.51.5.543
更新日期:1982-11-01 00:00:00
abstract::The effects of endothelin on systemic and renal hemodynamics in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were examined. Endothelin (500 ng i.v. +1,000 ng/hr per 300-g rat) elevated mean blood pressure by 13% (p less than 0.02) and decreased renal blood flow by 71% and glomerular filtrat...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.5.1370
更新日期:1989-11-01 00:00:00
abstract::Sinus node recovery time was compared to the recovery time of a slow atrioventricular junctional rhythm in each of the same seven pentobarbital anesthetized dogs. Recovery time and the first five cardiac cycles were examined after pacing atria and ventricles for 20, 40, and 60 seconds at four or more pacing cycle leng...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.1.182
更新日期:1985-07-01 00:00:00
abstract::Hypercholesterolemia induces atheroma formation, and the concentration of sphingomyelin is increased compared with that in the normal aortic intima-media. The aortic intima-media sphingomyelin concentration appears to increase exponentially with time on the cholesterol diet. Moreover, the entry rate of serum sphingomy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.2.294
更新日期:1975-02-01 00:00:00
abstract:RATIONALE:Adoptive transfer of cardiac progenitor cells (CPCs) has entered clinical application, despite limited mechanistic understanding of the endogenous response after myocardial infarction (MI). Extracellular matrix undergoes dramatic changes after MI and therefore might be linked to CPC-mediated repair. OBJECTIV...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301152
更新日期:2013-07-05 00:00:00
abstract::The bioactivity of nitric oxide (.NO) depends, in part, on its interaction with superoxide. Usually, superoxide dismutase (SOD) preserves .NO bioactivity by limiting the availability of superoxide. Ascorbic acid also effectively scavenges superoxide, but the extent to which this interaction is necessary for intact .NO...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.9.916
更新日期:1998-11-02 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:RATIONALE:Complementation of pluripotency genes may improve adult stem cell functions. OBJECTIVES:Here we show that clonally expandable, telomerase expressing progenitor cells can be isolated from peripheral blood of children. The surface marker profile of the clonally expanded cells is distinct from hematopoietic or ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.206045
更新日期:2010-04-16 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
abstract::Postnatal development of the mammalian heart is associated with changes in the population of isoforms of the thin filament proteins. We correlated the change in thin filament proteins, which occur in rabbit hearts between 5 days and 22 days of age, with changes in Ca2+ dependence of myofibrillar ATPase activity, force...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.5.1204
更新日期:1990-05-01 00:00:00
abstract::Cardiovascular aging is associated with decreased endothelial vasoreactivity and prolonged diastolic relaxation. As diminished NO signaling contributes to age-associated endothelial dysfunction, we tested the hypothesis that impaired NO signaling or bioactivity also contributes to slowed ventricular relaxation with ag...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.88.1.97
更新日期:2001-01-19 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::Coronary pressure-flow relations during autoregulated and vasodilated flow states were compared between eight dogs with renovascular hypertension and left ventricular hypertrophy and 12 normal dogs. Each relation was constructed from serial steady-state measurements of end-diastolic coronary pressure and flow during p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.224
更新日期:1989-07-01 00:00:00
abstract::Heart failure is associated with death of cardiomyocytes leading to loss of contractility. Previous studies using membrane-targeted Akt (myristolated-Akt), an enzyme involved in antiapoptotic signaling, showed inhibition of cell death and prevention of pathogenesis induced by cardiomyopathic stimuli. However, recent s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000124394.01180.BE
更新日期:2004-04-16 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::Basic calcium phosphate (BCP) crystal deposition underlies the development of arterial calcification. Inflammatory macrophages colocalize with BCP deposits in developing atherosclerotic lesions and in vitro can promote calcification through the release of TNF alpha. Here we have investigated whether BCP crystals can e...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000171451.88616.c2
更新日期:2005-06-24 00:00:00
abstract::To determine whether the attenuation in the growth capacity of myocytes in the overloaded aging heart is associated with an impairment in the activation of insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) in the stressed cells, large myocardial infarcts were produced in Fischer 344 rats at 4 and 16 month...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.78.4.536
更新日期:1996-04-01 00:00:00
abstract::Ca2+ influx through the L-type calcium channel (LTCC) induces Ca2+ release from the sarcoplasmic reticulum (SR) and maintains SR Ca2+ loading. Alterations in LTCC properties, their contribution to the blunted adrenergic responsiveness in failing hearts and their recovery after support with LV assist devices (LVAD) wer...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000033988.13062.7c
更新日期:2002-09-20 00:00:00
abstract:RATIONALE:Mutations in vascular endothelial growth factor (VEGF) receptor-3 (VEGFR3 or FLT4) cause Milroy disease, an autosomal dominant condition that presents with congenital lymphedema. Mutations in VEGFR3 are identified in only 70% of patients with classic Milroy disease, suggesting genetic heterogeneity. OBJECTIV...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.300350
更新日期:2013-03-15 00:00:00
abstract:RATIONALE:Remote ischemic conditioning (RIC) or ischemic postconditioning (PostC) may protect the myocardium from ischemia-reperfusion injury in patients with ST-segment-elevation myocardial infarction. OBJECTIVE:To determine whether combined intrahospital RIC and PostC or PostC alone in addition to primary percutaneo...
journal_title:Circulation research
pub_type: 杂志文章,随机对照试验
doi:10.1161/CIRCRESAHA.118.314500
更新日期:2019-05-10 00:00:00
abstract::Intracellular potassium activity in guinea pig left atria was measured using potassium ion-selective microelectrodes and conventional microelectrodes. The effects of extracellular potassium concentration and acetylcholine on both intracellular potassium activity and the relationship between the resting membrane potent...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.54.1.65
更新日期:1984-01-01 00:00:00