Abstract:
RATIONALE:Despite significant interest in bone marrow mononuclear cell (BMC) therapy for ischemic heart disease, current techniques have resulted in only modest benefits. However, selected patients have shown improvements after autologous BMC therapy, but the contributing factors are unclear. OBJECTIVE:The purpose of this study was to identify BMC characteristics associated with a reduction in infarct size after ST-segment-elevation-myocardial infarction. METHODS AND RESULTS:This prospective study comprised patients consecutively enrolled in the CCTRN TIME (Cardiovascular Cell Therapy Research Network Timing in Myocardial Infarction Evaluation) trial who agreed to have their BMCs stored and analyzed at the CCTRN Biorepository. Change in infarct size between baseline (3 days after percutaneous coronary intervention) and 6-month follow-up was measured by cardiac MRI. Infarct-size measurements and BMC phenotype and function data were obtained for 101 patients (mean age, 56.5 years; mean screening ejection fraction, 37%; mean baseline cardiac MRI ejection fraction, 45%). At 6 months, 75 patients (74.3%) showed a reduction in infarct size (mean change, -21.0±17.6%). Multiple regression analysis indicated that infarct size reduction was greater in patients who had a larger percentage of CD31(+) BMCs (P=0.046) and in those with faster BMC growth rates in colony-forming unit Hill and endothelial-colony forming cell functional assays (P=0.033 and P=0.032, respectively). CONCLUSIONS:This study identified BMC characteristics associated with a better clinical outcome in patients with segment-elevation-myocardial infarction and highlighted the importance of endothelial precursor activity in regenerating infarcted myocardium. Furthermore, it suggests that for these patients with segment-elevation-myocardial infarction, myocardial repair was more dependent on baseline BMC characteristics than on whether the patient underwent intracoronary BMC transplantation. CLINICAL TRIAL REGISTRATION INFORMATION URL:http://www.clinicaltrials.gov. Unique identifier: NCT00684021.
journal_name
Circ Resjournal_title
Circulation researchauthors
Schutt RC,Trachtenberg BH,Cooke JP,Traverse JH,Henry TD,Pepine CJ,Willerson JT,Perin EC,Ellis SG,Zhao DX,Bhatnagar A,Johnstone BH,Lai D,Resende M,Ebert RF,Wu JC,Sayre SL,Orozco A,Zierold C,Simari RD,Moyé L,Cogledoi
10.1161/CIRCRESAHA.116.304710subject
Has Abstractpub_date
2015-01-02 00:00:00pages
99-107issue
1eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.304710journal_volume
116pub_type
杂志文章,多中心研究,随机对照试验abstract::A selective history of the pathophysiological, structural, and metabolic changes found during an episode of severe myocardial ischemia in the canine heart is presented. The changes that cause ischemic injury to become irreversible are discussed in detail because these changes are the target of any successful therapy d...
journal_title:Circulation research
pub_type: 历史文章,杂志文章,评审
doi:10.1161/CIRCRESAHA.113.300987
更新日期:2013-08-02 00:00:00
abstract::Baroreceptor reflexes can be demonstrated during fetal life, but whether baroreceptors normally regulate fetal arterial pressure is unknown. This problem was addressed directly by measuring arterial pressure and analyzing its variation in eight unanesthetized fetal lambs throughout the last third of gestation, and com...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.52.5.580
更新日期:1983-05-01 00:00:00
abstract::Several time- and voltage-dependent ionic currents have been identified in cardiac pacemaker cells, including Na(+) current, L- and T-type Ca(2+) currents, hyperpolarization-activated cation current, and various types of delayed rectifier K(+) currents. Mathematical models have demonstrated that spontaneous action pot...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.res.87.2.88
更新日期:2000-07-21 00:00:00
abstract::The purpose of this study was to determine whether biphasic restitution of action potential duration (APD) in ventricular muscle permits the development of complex dynamic behavior. Such behavior is expected because of the steep ascending slope of restitution and the presence of a maximum. Action potentials recorded f...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.5.915
更新日期:1995-05-01 00:00:00
abstract::The rate of renin secretion from renal juxtaglomerular (JG) cells is the major determinant of the activity of the renin-angiotensin system. However, the mechanisms involved in the excretion and turnover of secretory granules in the JG cells remain obscure. Therefore, in the present study, the whole-cell patch-clamp te...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.8.929
更新日期:1999-04-30 00:00:00
abstract::Oxygen free radicals have the ability to oxidize cholesterol. However, nothing is known about the effects of cholesterol oxidation on ion transport in isolated myocardial membranes. The purpose of the present study was to investigate the effects of in situ oxidative modification of sarcolemmal cholesterol on Ca2+ flux...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.68.1.18
更新日期:1991-01-01 00:00:00
abstract::The deposition of platelets at the site of balloon angioplasty is thought to play a major role in the pathogenesis of restenosis. The antibody AZ-1, which binds to the rabbit platelet glycoprotein IIb/IIIa receptor and inhibits platelet function both in vitro and in vivo, was produced and tested in an experimental mod...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.2.268
更新日期:1994-08-01 00:00:00
abstract:RATIONALE:We previously reported that vascular endothelial growth factor (VEGF)-induced binding of VEGF receptor 2 (VEGFR2) to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2. However, the mole...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307679
更新日期:2016-03-18 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::The synthesis of an angiotensin II (A II) antagonist, sarcosyl1-cysteinyl(S-methyl)8-angiotensin II [Sar1-Cys(Me)8-A II], showing partial organ selectivity and properties of a noncompetitive antagonist, is described. The compound was found to be an extremely potent antagonist on vascular smooth muscle both in vitro (p...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.46.5.720
更新日期:1980-05-01 00:00:00
abstract::We have measured the apparent Ca2+ sensitivities of force development in skinned cardiac trabeculae at different sarcome lengths together with shifts in troponin (Tn) T subunits on specimens from the same hearts and drawn insights into the pathogenesis of myocardial dysfunction in the diabetic rat. The Ca(2+)-force re...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.4.600
更新日期:1995-04-01 00:00:00
abstract::Long QT syndrome (LQTS) type 3 (LQT3), typified by the DeltaKPQ mutation (LQT3 mutation in which amino acid residues 1505 to 1507 [KPQ] are deleted), is caused by increased sodium entry during the action potential plateau resulting from mutation-altered inactivation of the Na(v)1.5 channel. Although rare, LQT3 is the ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000251305.25604.b0
更新日期:2006-11-24 00:00:00
abstract::3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) can exert beneficial effects independently of serum cholesterol reduction by increasing the bioavailability of nitric oxide. However, it is unclear whether statins can exert such effects directly on cardiac myocytes and whether mitochondria...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000097262.21507.DF
更新日期:2003-10-17 00:00:00
abstract::C-reactive protein (CRP), a characteristic inflammatory marker, is a powerful predictor of cardiovascular events. Recent data suggest that CRP may also promote atherogenesis through inducing endothelial dysfunction. Lectin-like oxidized low-density lipoprotein (oxLDL) receptor-1 (LOX-1) is a newly identified endotheli...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000147309.54227.42
更新日期:2004-10-29 00:00:00
abstract::Large-conductance Ca2+-dependent K+ channels (KCa), which are abundant on the sarcolemma of vascular myocytes, provide negative feedback via membrane hyperpolarization that limits Ca2+ entry through L-type Ca2+ channels (ICaL). We hypothesize that local accumulation of subsarcolemmal Ca2+ during ICaL openings amplifie...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.84.9.1032
更新日期:1999-05-14 00:00:00
abstract::Endothelial cells, either in vivo or freshly isolated, respond when exposed to muscarinic agonists with an increase in cytosolic free calcium concentration ([Ca2+]i) and release of endothelium-derived relaxing factor (EDRF). When placed in culture, however, endothelial cells rapidly lose these responses, which may be ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.234
更新日期:1992-02-01 00:00:00
abstract::Shear stress-induced activation of endothelial ion channels, one of the earliest responses to flow, is implicated in mechano-signal transduction that results in the regulation of vascular tone. The effects of laminar flow on endothelial membrane potential were studied in vitro using both fluorescent potentiometric dye...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.9.820
更新日期:1999-10-29 00:00:00
abstract::Vascular endothelial growth factor (VEGF) expression is upregulated by hypoxia-inducible factor-1 (HIF-1) in ischemic tissues and growing tumors. Normally, HIF-1 activity depends on the amount of HIF-1alpha subunit, which is tightly regulated by the oxygen tension. In the myocardium, VEGF expression has been shown to ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh0202.104923
更新日期:2002-02-08 00:00:00
abstract::Aldose reductase (AR), a member of the aldo-keto reductase superfamily, has been shown to metabolize toxic aldehydes generated by lipid peroxidation, suggesting that it may serve as an antioxidant defense. To investigate its role in the late phase of ischemic preconditioning (PC), conscious rabbits underwent 6 cycles ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000029970.97247.57
更新日期:2002-08-09 00:00:00
abstract::Oxidation converts low-density lipoprotein (LDL) into a cytotoxin in vitro. Oxidized LDL exists in vivo in atherosclerotic lesions and possibly in plasma. Many cell functions are altered in vitro by oxidized LDL, but few have been examined in vivo. To test whether oxidized LDL could injure endothelial cells and alter ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.1.37
更新日期:1997-01-01 00:00:00
abstract:RATIONALE:Mitochondria, although required for cellular ATP production, are also known to have other important functions that may include modulating cellular responses to environmental stimuli. However, the mechanisms whereby mitochondria impact cellular phenotype are not yet clear. OBJECTIVE:To determine how mitochond...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.113.301319
更新日期:2013-09-13 00:00:00
abstract::The accumulation of inositol 1,4,5-trisphosphate (IP3) after hormonal stimulation has a physiological role, possibly by alteration of Ca2+ levels in cardiac myocyte. However, this accumulation has not been studied under pathophysiological conditions. In this report, we examine phosphatidylinositol metabolism during ce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.72.5.966
更新日期:1993-05-01 00:00:00
abstract::Although functional coupling between protein kinase Cepsilon (PKCepsilon) and mitochondria has been implicated in the genesis of cardioprotection, the signal transduction mechanisms that enable this link and the identities of the mitochondrial proteins modulated by PKCepsilon remain unknown. Based on recent evidence t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000069215.36389.8D
更新日期:2003-05-02 00:00:00
abstract::This study investigated the possible roles of strongly binding myosin crossbridges in determining loaded shortening and power output in cardiac myocytes. Single skinned cardiac myocytes were attached between a force transducer and position motor, and shortening velocities were measured over a range of loads during var...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.87.9.768
更新日期:2000-10-27 00:00:00
abstract::We have previously demonstrated that urokinase-type plasminogen activator (uPA) is highly expressed in the aneurysmal segment of the abdominal aorta (AAA) in apolipoprotein E-deficient (apoE-/-) mice treated with angiotensin II (Ang II). In the present study, we tested the hypothesis that uPA is essential for AAA form...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000061571.49375.E1
更新日期:2003-03-21 00:00:00
abstract::In adult mammals, massive sudden loss of cardiomyocytes after infarction overwhelms the limited regenerative capacity of the myocardium, resulting in the formation of a collagen-based scar. Necrotic cells release danger signals, activating innate immune pathways and triggering an intense inflammatory response. Stimula...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.116.303577
更新日期:2016-06-24 00:00:00
abstract::Atrial tissue expresses both connexin 40 (Cx40) and 43 (Cx43) proteins. To assess the relative roles of Cx40 and Cx43 in atrial electrical propagation, we synthesized cultured strands of atrial myocytes derived from mice with genetic deficiency in Cx40 or Cx43 expression and measured propagation velocity (PV) by high-...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000250607.34498.b4
更新日期:2006-11-24 00:00:00
abstract::The realization of regenerative cardiac medicine depends on the availability of cardiomyocytes in sufficient numbers for transplantation of cardiac tissue and the accompanying blood vessels. Embryonic stem (ES) cells, bone marrow (BM) stem cells, and tissue-derived stem cells are all potential cell sources. Although E...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000218272.18669.6e
更新日期:2006-04-28 00:00:00
abstract::In studies that attempt to measure intracellular calcium [( Ca2+]i) in the intact heart with the calcium indicator indo 1-AM, a fundamental assumption is that the signals report changes in myocyte [Ca2+]i. We studied isolated perfused rabbit hearts loaded with the calcium probe indo 1-AM and recorded surface fluoresce...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.2.415
更新日期:1990-08-01 00:00:00
abstract::We compared the effects of the newer inotropic drugs, pimobendan (UD-CG 115 BS) and milrinone (Win 47203), on the electrical, mechanical and biochemical activity of intact and detergent-skinned preparations of cardiac muscle. Both of these agents increased contractile force of guinea pig papillary muscle preparations ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.63.5.911
更新日期:1988-11-01 00:00:00