Abstract:
RATIONALE:Gamma aminobutyric acid (GABA), a neurotransmitter of the central nervous system, is found in the systemic circulation of humans at a concentration between 0.5 and 3 μmol/L. However, the potential source of circulating GABA and its significance on the vascular system remains unknown. We hypothesized that endothelial cells (ECs) may synthesize and release GABA to modulate some functions in the EC and after its release into the circulation. OBJECTIVE:To assess whether GABA is synthesized and released by the EC and its potential functions. METHODS AND RESULTS:Utilizing the human umbilical vein ECs and aortic ECs, we demonstrated for the first time that ECs synthesize and release GABA from [1-(14)C]glutamate. Localization of GABA and the presence of the GABA-synthesizing enzyme, glutamic acid decarboxylase in EC were confirmed by immunostaining and immunoblot analysis, respectively. The presence of GABA was further confirmed by immunohistochemistry in the EC lining the human coronary vessel. EC-derived GABA regulated the key mechanisms of ATP synthesis, fatty acid, and pyruvate oxidation in EC. GABA protected EC by inhibiting the reactive oxygen species generation and prevented monocyte adhesion by attenuating vascular cell adhesion molecule -1 and monocyte chemoattractant protein-1 expressions. GABA had no relaxing effect on rat aortic rings. GABA exhibited a dose-dependent fall in blood pressure. However, the fall in BP was abolished after pretreatment with pentolinium. CONCLUSIONS:Our findings indicate novel potential functions of endothelium-derived GABA.
journal_name
Circ Resjournal_title
Circulation researchauthors
Sen S,Roy S,Bandyopadhyay G,Scott B,Xiao D,Ramadoss S,Mahata SK,Chaudhuri Gdoi
10.1161/CIRCRESAHA.116.308645subject
Has Abstractpub_date
2016-08-19 00:00:00pages
621-34issue
5eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.308645journal_volume
119pub_type
杂志文章abstract::This study investigations the phenomenon of sustained mechanical alternans (SMA) through the use of quantitative criteria. Discrete analysis is used to demonstrate that the hemodynamic variables during SMA are governed by a simple mathematical relation. The analysis shows that the value of the slope created by the two...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.69.1.26
更新日期:1991-07-01 00:00:00
abstract::Over the last 4 decades, heart transplantation (HTx) has evolved as a mainstream therapy for heart failure. Approximately half of patients needing HTx have organ failure consequent to atherosclerosis. Despite advances in immunosuppressive drugs, long-term success of HTx is limited by the development of a particular ty...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/01.RES.0000246086.93555.f3
更新日期:2006-10-13 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:RATIONALE:Our insights into physiological and pathophysiological cardiac excitation-contraction coupling has greatly benefited from significant advancement in optical technologies such as high-speed confocal microscopy. This has pushed pixel dwell times into the time domain of nanoseconds, resulting in low signal-to-no...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.112.266403
更新日期:2012-06-22 00:00:00
abstract::The transcription factor signal transducer and activator of transcription 3 (STAT3) participates in a wide variety of physiological processes and directs seemingly contradictory responses such as proliferation and apoptosis. To elucidate its role in the heart, we generated mice harboring a cardiomyocyte-restricted kno...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000134921.50377.61
更新日期:2004-07-23 00:00:00
abstract::Trimetazidine is a clinically effective antianginal agent that has no negative inotropic or vasodilator properties. Although it is thought to have direct cytoprotective actions on the myocardium, the mechanism(s) by which this occurs is as yet undefined. In this study, we determined what effects trimetazidine has on b...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.86.5.580
更新日期:2000-03-17 00:00:00
abstract:RATIONALE:Lymphatic vessels in the respiratory tract normally mature into a functional network during the neonatal period, but under some pathological conditions they can grow as enlarged, dilated sacs that result in the potentially lethal condition of pulmonary lymphangiectasia. OBJECTIVE:We sought to determine wheth...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.114.303119
更新日期:2014-02-28 00:00:00
abstract::A new protocol has been developed for selective removal of the endothelium from the arteries of the perfused rat hind-limb preparation. The hind limb was perfused with oxygenated Krebs-Ringer bicarbonate solution with a combination of high flow and timed air bubbles (2 minutes at high flow followed by 5 minutes of air...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.64.6.1190
更新日期:1989-06-01 00:00:00
abstract::We have previously demonstrated pressure-dependent membrane depolarization and action potential generation in cat cerebral arteries. It was the purpose of this study to examine and compare the membrane electrical responses to increasing transmural pressure in spontaneously hypertensive rats with those of their normote...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.57.2.319
更新日期:1985-08-01 00:00:00
abstract::We quantitated phasic epimyocardial microcirculatory coronary blood flow velocity patterns in the beating left ventricle. Using a newly developed floating objective and high-speed cinematography, red cell velocities in small arterioles, capillaries, and small venules and microvascular diameters in the superficial laye...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.59.6.704
更新日期:1986-12-01 00:00:00
abstract::Changes in cardiac filling pressure (central venous pressure) were measured following carotid occlusion and infusions of catecholamines in awake dogs while cardiac output was held constant. After carotid occlusion in dogs with vagi blocked, central venous pressure increased about 0.8 mm Hg (an estimated decrease in va...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.4.440
更新日期:1984-10-01 00:00:00
abstract::To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers. Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent s...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.58.2.209
更新日期:1986-02-01 00:00:00
abstract::In newborn lambs, pulmonary prostacyclin (PGI2) production increases acutely in response to low oxygen. We tested the hypothesis that decreased oxygenation directly stimulates PGI2 synthesis in arterial segments and cultured endothelial cells from newborn lamb intrapulmonary arteries. In segments studied at PO2 of 680...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.75.1.33
更新日期:1994-07-01 00:00:00
abstract::A series of new phenylethanolamines with 2-methoxy and/or 4-methyl, 4-chloro, or 4-bromo ring substituents and either N-isopropyl or N-tert butyl substituents have been synthesized and tested for beta 1- and beta 2-adrenoceptor blocking activity using isolated guinea pig atrial and tracheal preparations. Each of the d...
journal_title:Circulation research
pub_type: 杂志文章
doi:
更新日期:1980-06-01 00:00:00
abstract::To determine the relative importance of protein degradation in the development of starvation-induced cardiac atrophy, in vivo fractional synthetic rates of total cardiac protein, myosin heavy chain, actin, light chain 1, and light chain 2 were measured in fed and fasted rabbits by continuous infusion of [3H] leucine. ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.60.6.933
更新日期:1987-06-01 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::Recent pharmacological studies have shown that perivascular nerves can influence the development and function of vascular endothelial cells (ECs). However, morphological studies have not yet been carried out to investigate whether these functional changes are associated with changes in vasoactive substances in ECs. We...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.79.2.317
更新日期:1996-08-01 00:00:00
abstract:RATIONALE:Thioredoxin (Trx)1 inhibits pathological cardiac hypertrophy. MicroRNAs (miRNAs) are small noncoding RNAs that downregulate posttranscriptional expression of target molecules. OBJECTIVES:We investigated the role of miRNAs in mediating the antihypertrophic effect of Trx1 on angiotensin II (Ang II)-induced car...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.110.228437
更新日期:2011-02-04 00:00:00
abstract::Bone marrow-derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial cells (ECs) or indirectly through growth factor release. To examine these possibilities under physiological conditions, we developed a model of hypoxia-mediated angiogenesis ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000189259.69645.25
更新日期:2005-11-11 00:00:00
abstract::Life threatening ventricular arrhythmias leading to sudden cardiac death are a major cause of morbidity and mortality. In the absence of structural heart disease, these arrhythmias, especially in the younger population, are often an outcome of genetic defects in specialized membrane proteins called ion channels. In th...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.118.311209
更新日期:2018-07-06 00:00:00
abstract::The inward current ("oscillatory current") which may be present after the end of a depolarizing clamp was studied in sheep cardiac Purkinje fibers by means of a voltage-clamp method. The following results were obtained. In order to appear, the oscillatory current (Ios) requires a previous depolarization to approximate...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.48.5.618
更新日期:1981-05-01 00:00:00
abstract::The identification of nitric oxide ((*)NO) as an endogenously produced free radical mediator of endothelial-dependent relaxation and host defense has fundamentally changed concepts of cell signal transduction. Ligand-receptor oriented paradigms of cell signaling were originally centered on the concept of a high affini...
journal_title:Circulation research
pub_type: 杂志文章,评审
doi:10.1161/CIRCRESAHA.109.202077
更新日期:2009-09-11 00:00:00
abstract::Blocking brain mineralocorticoid receptors (MRs) reduces the high circulating levels of tumor necrosis factor (TNF)-alpha in heart failure (HF) rats. TNF-alpha and other proinflammatory cytokines activate neurons in the paraventricular nucleus (PVN) of hypothalamus, including corticotropin-releasing hormone (CRH) neur...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000244092.95152.86
更新日期:2006-09-29 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::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::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 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:RATIONALE:Unlike conventional dendritic cells, plasmacytoid DCs (PDC) are poor in antigen presentation and critical for type I interferon response. Though proposed to be present in human atherosclerotic lesions, their role in atherosclerosis remains elusive. OBJECTIVE:To investigate the role of PDC in atherosclerosis....
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.111.256529
更新日期:2011-12-09 00:00:00
abstract::Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit bot...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.0000041418.51906.57
更新日期:2002-11-15 00:00:00
abstract::The endothelial cell membrane glycoprotein thrombomodulin (TM) plays a critical role in the regulation of coagulation. TM is an essential cofactor in protein C activation by thrombin, and a direct inhibitor of thrombin-induced platelet activation and fibrinogen clotting. Protease nexin-1 (PN-1) is a serpin synthesized...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000265066.92923.ee
更新日期:2007-04-27 00:00:00