Abstract:
RATIONALE:Pulmonary arterial hypertension (PAH) remains a progressive and eventually lethal disease characterized by increased pulmonary vascular resistance because of loss of functional lung microvasculature, primarily at the distal (intracinar) arteriolar level. Cell-based therapies offer the potential to repair and regenerate the lung microcirculation and have shown promise in preclinical evaluation in experimental models of PAH. OBJECTIVE:The Pulmonary Hypertension and Angiogenic Cell Therapy (PHACeT) trial was a phase 1, dose-escalating clinical study of the tolerability of culture-derived endothelial progenitor cells, transiently transfected with endothelial nitric oxide synthase, in patients with PAH refractory to PAH-specific therapies. METHODS AND RESULTS:Seven to 50 million endothelial nitric oxide synthase-transfected endothelial progenitor cells, divided into 3 doses on consecutive days, were delivered into the right atrium via a multiport pulmonary artery catheter during continuous hemodynamic monitoring in an intensive care unit setting. Seven patients (5 women) received treatment from December 2006 to March 2010. Cell infusion was well tolerated, with no evidence of short-term hemodynamic deterioration; rather, there was a trend toward improvement in total pulmonary resistance during the 3-day delivery period. However, there was 1 serious adverse event (death) which occurred immediately after discharge in a patient with severe, end stage disease. Although there were no sustained hemodynamic improvements at 3 months, 6-minute walk distance was significantly increased at 1, 3, and 6 months. CONCLUSION:Delivery of endothelial progenitor cells overexpressing endothelial nitric oxide synthase was tolerated hemodynamically in patients with PAH. Furthermore, there was evidence of short-term hemodynamic improvement, associated with long-term benefits in functional and quality of life assessments. However, future studies are needed to further establish the efficacy of this therapy. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00469027.
journal_name
Circ Resjournal_title
Circulation researchauthors
Granton J,Langleben D,Kutryk MB,Camack N,Galipeau J,Courtman DW,Stewart DJdoi
10.1161/CIRCRESAHA.114.305951subject
Has Abstractpub_date
2015-09-11 00:00:00pages
645-54issue
7eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.114.305951journal_volume
117pub_type
杂志文章,多中心研究abstract::Computer simulations and nonlinear dynamics have provided invaluable tools for illuminating the underlying mechanisms of cardiac arrhythmias. Here, we review how this approach has led to major insights into the mechanisms of spatially discordant alternans, a key arrhythmogenic factor predisposing the heart to re-entry...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000224540.97431.f0
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abstract:RATIONALE:The activation of the Smad2 signaling pathway is thought to play an important role in human aneurysmal diseases as described by an important body of research. We previously showed that constitutive Smad2 activation is associated with Smad2 mRNA overexpression in aneurysmal vascular smooth muscle cells (VSMCs)...
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abstract::In the early (3-day) stage of development, long-lasting openings of the L-type Ca2+ channels (mode 2) occur in embryonic chick heart cells. Since mode-2 behavior is infrequently observed in adult heart cells of other species, in the present study, developmental change in behavior of the Ca2+ channel was examined in yo...
journal_title:Circulation research
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doi:10.1161/01.res.71.2.376
更新日期:1992-08-01 00:00:00
abstract::Herein, we show that the paired-related homeobox gene, Prx1, is required for lung vascularization. Initial studies revealed that Prx1 localizes to differentiating endothelial cells (ECs) within the fetal lung mesenchyme, and later within ECs forming vascular networks. To begin to determine whether Prx1 promotes EC dif...
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abstract::Previous studies have demonstrated that in adult rats with chronic hyponatremia, both symptoms of encephalopathy and mortality largely depend upon the gender of the animal and the presence of elevated plasma levels of vasopressin (AVP). Since effects of AVP on blood vessels may be gender dependent, the present study w...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.4.551
更新日期:1995-04-01 00:00:00
abstract::Hibernating myocardium, characterized by reductions in flow and function at rest, has limited contractile reserve in response to increases in external workload. We hypothesized that this attenuation of function reflects an adaptive downregulation that prevents the development of metabolic evidence of ischemia during s...
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pub_type: 杂志文章
doi:10.1161/01.res.0000049104.57549.03
更新日期:2003-01-10 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 ...
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1976-06-01 00:00:00
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更新日期:2010-04-30 00:00:00
abstract:RATIONALE:Individuals with naturally occurring loss-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations experience reduced low-density lipoprotein cholesterol levels and protection against cardiovascular disease. OBJECTIVE:The goal of this study was to assess whether genome editing using a clus...
journal_title:Circulation research
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doi:10.1161/CIRCRESAHA.115.304351
更新日期:2014-08-15 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.73.5.839
更新日期:1993-11-01 00:00:00
abstract::We measured pressure-volume curves in nine excised dog ventricles and stress-strain curves in two to five muscle specimens from each ventricle to verify a derived formula that relates muscle stiffness to the ventricular pressure-volume curve. The assumptions underlying this formula are: (1) the ventricle is a uniform ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.37.6.787
更新日期:1975-12-01 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...
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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::Mitochondrial quality is a crucial determinant of cell viability, and mitochondrial autophagy plays a central role in this control mechanism. Based on studies in yeast, numerous investigations of this process have been conducted, and the framework of mammalian mitochondrial autophagy is progressively appearing. Howeve...
journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2015-04-10 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.304056
更新日期:2014-09-12 00:00:00
abstract:RATIONALE:Sustained cardiac hypertrophy is often accompanied by maladaptive cardiac remodeling leading to decreased compliance and increased risk for heart failure. Maladaptive hypertrophy is considered to be a therapeutic target for heart failure. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have various biolo...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.302476
更新日期:2014-04-25 00:00:00
abstract::Angiotensin II (Ang II) plays an important role in post-myocardial infarction (MI) remodeling. Most Ang II effects related to remodeling involve activation of the type 1 receptor (AT(1)). Although the AT(1) receptor is upregulated on cardiac fibroblasts post-MI, little is known about the mechanisms involved in the pro...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.3.272
更新日期:1999-08-06 00:00:00
abstract::To determine whether opioid receptors (ORs) are involved in the delayed cardioprotection of ischemic preconditioning (IP), the effect of severe metabolic inhibition (MI) with a glucose-free buffer that contained sodium cyanide and 2-deoxy-D-glucose on the viability of isolated rat ventricular myocytes was first determ...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1999-06-25 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2018-04-27 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1988-12-01 00:00:00
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pub_type: 杂志文章
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更新日期:1993-08-01 00:00:00
abstract::Recent studies have suggested a proangiogenic effect of angiotensin-converting enzyme (ACE) inhibition. We hypothesized that such a proangiogenic effect of ACE inhibition may be mediated, in part, by bradykinin (BK) B(2)-receptor pathway. This study therefore examined the neovascularization induced by ACE inhibitor tr...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh2001.097691
更新日期:2001-10-12 00:00:00
abstract::Vascular calcification is a common finding in atherosclerosis and a serious problem in diabetic and uremic patients. Because of the correlation of hyperphosphatemia and vascular calcification, the ability of extracellular inorganic phosphate levels to regulate human aortic smooth muscle cell (HSMC) culture mineralizat...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2000-09-29 00:00:00
abstract:RATIONALE:POSTN (Periostin) is an ECM (extracellular matrix) protein involved in tissue remodeling in response to injury and a contributing factor in tumorigenesis, suggesting that POSTN plays a role in the pathogenesis of pulmonary hypertension (PH). OBJECTIVE:We aimed to gain insight into the mechanistic contributio...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.120.316943
更新日期:2020-10-09 00:00:00
abstract::We determined the extent of convergence of preganglionic fibers from the right and left vagus nerves on postganglionic neurons that supply the sinoatrial node in chloralose-anesthetized dogs. We administered hemicholinium-3 and stimulated the right vagus nerve at a high frequency to deplete acetylcholine from the post...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.67.3.556
更新日期:1990-09-01 00:00:00
abstract:RATIONALE:Necrosis is one of the main forms of cardiomyocyte death in heart disease. Recent studies have demonstrated that certain types of necrosis are regulated and programmed dependent on the activation of receptor-interacting serine/threonine-protein kinase (RIPK) 1 and 3 which may be negatively regulated by Fas-as...
journal_title:Circulation research
pub_type: 杂志文章
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更新日期:2015-07-31 00:00:00
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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::High-density lipoprotein (HDL) is a complex mixture of lipoproteins that is associated with many minor proteins and lipids that influence the function of HDL. Although HDL is a promising marker and potential therapeutic target based on its epidemiological data and the effects of healthy HDL in vitro in endothelial cel...
journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2014-01-03 00:00:00
abstract::The type 1B angiotensin II (AT1B) receptor cloned from rat kidney was stably expressed in Chinese hamster ovary cells. The stably expressed receptor was characterized by radioligand binding studies and functional coupling to inositol 1,4,5-triphosphate (IP3) formation. Exposure of cells expressing the AT1B receptor to...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.77.2.239
更新日期:1995-08-01 00:00:00