Pivotal role for endothelial tetrahydrobiopterin in pulmonary hypertension.

Abstract:

BACKGROUND:Pulmonary hypertension is a fatal disease characterized by vasoconstriction and vascular remodeling. Loss of endothelial nitric oxide bioavailability is implicated in pulmonary hypertension pathogenesis. Recent evidence suggests that the cofactor tetrahydrobiopterin (BH4) is an important regulator of nitric oxide synthase enzymatic function. METHODS AND RESULTS:In the hph-1 mouse with deficient BH4 biosynthesis, BH4 deficiency caused pulmonary hypertension, even in normoxic conditions, and greatly increased susceptibility to hypoxia-induced pulmonary hypertension. In contrast, augmented BH4 synthesis in the endothelium, by targeted transgenic overexpression of GTP-cyclohydrolase I (GCH), prevented hypoxia-induced pulmonary hypertension. Furthermore, specific augmentation of endothelial BH4 in hph-1 mice by crossing with GCH transgenic mice rescued pulmonary hypertension induced by systemic BH4 deficiency. Lung BH4 availability controlled pulmonary vascular tone, right ventricular hypertrophy, and vascular structural remodeling in a dose-dependent manner in both normoxia and hypoxia. Furthermore, BH4 availability had striking effects on the immediate vasoconstriction response to acute hypoxia. These effects of BH4 were mediated through the regulation of nitric oxide compared with superoxide synthesis by endothelial nitric oxide synthase. CONCLUSIONS:Endothelial BH4 availability is essential for maintaining pulmonary vascular homeostasis, is a critical mediator in the pathogenesis of pulmonary hypertension, and is a novel therapeutic target.

journal_name

Circulation

journal_title

Circulation

authors

Khoo JP,Zhao L,Alp NJ,Bendall JK,Nicoli T,Rockett K,Wilkins MR,Channon KM

doi

10.1161/01.CIR.0000162470.26840.89

subject

Has Abstract

pub_date

2005-04-26 00:00:00

pages

2126-33

issue

16

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000162470.26840.89

journal_volume

111

pub_type

杂志文章
  • Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association.

    abstract:BACKGROUND:Cardiovascular disease (CVD) is the leading cause of death in the United States and is responsible for 17% of national health expenditures. As the population ages, these costs are expected to increase substantially. METHODS AND RESULTS:To prepare for future cardiovascular care needs, the American Heart Asso...

    journal_title:Circulation

    pub_type: 共识发展会议,杂志文章

    doi:10.1161/CIR.0b013e31820a55f5

    authors: Heidenreich PA,Trogdon JG,Khavjou OA,Butler J,Dracup K,Ezekowitz MD,Finkelstein EA,Hong Y,Johnston SC,Khera A,Lloyd-Jones DM,Nelson SA,Nichol G,Orenstein D,Wilson PW,Woo YJ,American Heart Association Advocacy Coordinating

    更新日期:2011-03-01 00:00:00

  • Comparative effects of nitroglycerin, nifedipine and metoprolol on regional left ventricular function in patients with one-vessel coronary disease.

    abstract::To compare acute effects of nitroglycerin (0.8 mg sublingually), nifedipine (5 ng/kg/min i.v.) and metoprolol (0.15 mg/kg i.v.) on normal, ischemic and scarred myocardial segments in man, we performed simultaneous hemodynamic and radionuclide measurements of left ventricular functions. Sixteen patients with isolated l...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1161/01.cir.67.2.291

    authors: Pfisterer M,Glaus L,Burkart F

    更新日期:1983-02-01 00:00:00

  • Outcomes and long-term survival for patients undergoing mitral valve repair versus replacement: effect of age and concomitant coronary artery bypass grafting.

    abstract:BACKGROUND:A paucity of literature is available on the effects of age and coronary artery bypass grafting (CABG) on the outcomes of patients undergoing mitral valve (MV) repair versus replacement. METHODS AND RESULTS:A matched study was performed using prospectively collected data from the Emory cardiovascular databas...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000079169.15862.13

    authors: Thourani VH,Weintraub WS,Guyton RA,Jones EL,Williams WH,Elkabbani S,Craver JM

    更新日期:2003-07-22 00:00:00

  • Improved efficiency of treadmill exercise testing using a multiple lead ECG system and basic hemodynamic exercise response.

    abstract::One hundred consecutive men with a normal ECG at rest had a maximal treadmill test using 14 leads during and post-exercise. Coronary arteriography performed the following day revealed coronary stenoses greater than or equal to 70% in 66 patients. Test results obtained from a V5 lead were compared to different lead com...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.57.1.71

    authors: Chaitman BR,Bourassa MG,Wagniart P,Corbara F,Ferguson RJ

    更新日期:1978-01-01 00:00:00

  • Survivin-induced abnormal ploidy contributes to cystic kidney and aneurysm formation.

    abstract:BACKGROUND:Cystic kidneys and vascular aneurysms are clinical manifestations seen in patients with polycystic kidney disease, a cilia-associated pathology (ciliopathy). Survivin overexpression is associated with cancer, but the clinical pathology associated with survivin downregulation or knockout has never been studie...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.113.005746

    authors: Aboualaiwi WA,Muntean BS,Ratnam S,Joe B,Liu L,Booth RL,Rodriguez I,Herbert BS,Bacallao RL,Fruttiger M,Mak TW,Zhou J,Nauli SM

    更新日期:2014-02-11 00:00:00

  • Experimental model of single ventricle. Influence of carbon dioxide on pulmonary vascular dynamics.

    abstract:BACKGROUND:Important in the postoperative management of neonates with single-ventricle complexes, such as hypoplastic left heart syndrome and pulmonary atresia with intact ventricular septum, is the fact that the pulmonary circulation is connected to the systemic circulation via a shunt. The distribution of flow to the...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Mora GA,Pizarro C,Jacobs ML,Norwood WI

    更新日期:1994-11-01 00:00:00

  • Brachial artery flow-mediated dilation and asymmetrical dimethylarginine in the cardiovascular risk in young Finns study.

    abstract:BACKGROUND:Elevated asymmetrical dimethylarginine (ADMA) is a novel risk factor for atherosclerosis that may impair endothelial function by interfering with endothelial nitric oxide synthesis. To gain insight into the effects of ADMA on systemic endothelial function, we examined the association between ADMA and brachia...

    journal_title:Circulation

    pub_type: 杂志文章,多中心研究

    doi:10.1161/CIRCULATIONAHA.107.690016

    authors: Juonala M,Viikari JS,Alfthan G,Marniemi J,Kähönen M,Taittonen L,Laitinen T,Raitakari OT

    更新日期:2007-09-18 00:00:00

  • Prognostic value of lead V1 ST elevation during acute inferior myocardial infarction.

    abstract:BACKGROUND:Lead V(1) directly faces the right ventricle and may exhibit ST elevation during an acute inferior myocardial infarction when the right ventricle is also involved. Leads V(1) and V(3) indirectly face the posterolateral left ventricle, and ST depression ("mirror-image" ST elevation) in V(1) through V(3) may r...

    journal_title:Circulation

    pub_type: 杂志文章,随机对照试验

    doi:10.1161/CIRCULATIONAHA.109.924068

    authors: Wong CK,Gao W,Stewart RA,French JK,Aylward PE,Benatar J,White HD,Hirulog and Early Reperfusion or Occlusion-2 Investigators.

    更新日期:2010-08-03 00:00:00

  • Standardized End Point Definitions for Coronary Intervention Trials: The Academic Research Consortium-2 Consensus Document.

    abstract::The Academic Research Consortium (ARC)-2 initiative revisited the clinical and angiographic end point definitions in coronary device trials, proposed in 2007, to make them more suitable for use in clinical trials that include increasingly complex lesion and patient populations and incorporate novel devices such as bio...

    journal_title:Circulation

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCULATIONAHA.117.029289

    authors: Garcia-Garcia HM,McFadden EP,Farb A,Mehran R,Stone GW,Spertus J,Onuma Y,Morel MA,van Es GA,Zuckerman B,Fearon WF,Taggart D,Kappetein AP,Krucoff MW,Vranckx P,Windecker S,Cutlip D,Serruys PW,Academic Research Consortium

    更新日期:2018-06-12 00:00:00

  • Mechanism of atrial sounds in atrial fibrillation. Phonoechocardiographic correlation. Report of a case.

    abstract::Audible atrial sounds were noted in a patient with congestive cardiomyopathy and atrial fibrillation with slow ventricular rate. Oscillatory motion of similar periodicity as fibrillation waves in the ECG and the sounds in the phonocardiogram was demonstrated in aortic and left ventricular walls, mitral, tricuspid and ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.53.3.569

    authors: Bamrah VS,Hughes CV,Tristani FE

    更新日期:1976-03-01 00:00:00

  • Acute coronary care in the elderly, part I: Non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Ger

    abstract:BACKGROUND:Age is an important determinant of outcomes for patients with acute coronary syndromes (ACS); however, community practice reveals a disproportionately lower use of cardiovascular medications and invasive treatment even among elderly patients with ACS who would stand to benefit. Reasons include limited trial ...

    journal_title:Circulation

    pub_type: 杂志文章,评审

    doi:10.1161/CIRCULATIONAHA.107.182615

    authors: Alexander KP,Newby LK,Cannon CP,Armstrong PW,Gibler WB,Rich MW,Van de Werf F,White HD,Weaver WD,Naylor MD,Gore JM,Krumholz HM,Ohman EM,American Heart Association Council on Clinical Cardiology.,Society of Geriatric Cardiology

    更新日期:2007-05-15 00:00:00

  • Disruption of striated preferentially expressed gene locus leads to dilated cardiomyopathy in mice.

    abstract:BACKGROUND:The striated preferentially expressed gene (Speg) generates 4 different isoforms through alternative promoter use and tissue-specific splicing. Depending on the cell type, Speg isoforms may serve as markers of striated or smooth muscle differentiation. METHODS AND RESULTS:To elucidate function of Speg gene ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.108.799536

    authors: Liu X,Ramjiganesh T,Chen YH,Chung SW,Hall SR,Schissel SL,Padera RF Jr,Liao R,Ackerman KG,Kajstura J,Leri A,Anversa P,Yet SF,Layne MD,Perrella MA

    更新日期:2009-01-20 00:00:00

  • Effect of baseline or changes in adrenergic activity on clinical outcomes in the beta-blocker evaluation of survival trial.

    abstract:BACKGROUND:Adrenergic activation is thought to be an important determinant of outcome in subjects with chronic heart failure (CHF), but baseline or serial changes in adrenergic activity have not been previously investigated in a large patient sample treated with a powerful antiadrenergic agent. METHODS AND RESULTS:Sys...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验

    doi:10.1161/01.CIR.0000141297.50027.A4

    authors: Bristow MR,Krause-Steinrauf H,Nuzzo R,Liang CS,Lindenfeld J,Lowes BD,Hattler B,Abraham WT,Olson L,Krueger S,Thaneemit-Chen S,Hare JM,Loeb HS,Domanski MJ,Eichhorn EJ,Zelis R,Lavori P

    更新日期:2004-09-14 00:00:00

  • Randomized study of the crush technique versus provisional side-branch stenting in true coronary bifurcations: the CACTUS (Coronary Bifurcations: Application of the Crushing Technique Using Sirolimus-Eluting Stents) Study.

    abstract:BACKGROUND:Sirolimus-eluting stents have been reported to be effective in the treatment of coronary bifurcations. Still, it has not been fully clarified which strategy would provide the best results with true bifurcation lesions. METHODS AND RESULTS:The CACTUS trial (Coronary bifurcations: Application of the Crushing ...

    journal_title:Circulation

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1161/CIRCULATIONAHA.108.808402

    authors: Colombo A,Bramucci E,Saccà S,Violini R,Lettieri C,Zanini R,Sheiban I,Paloscia L,Grube E,Schofer J,Bolognese L,Orlandi M,Niccoli G,Latib A,Airoldi F

    更新日期:2009-01-06 00:00:00

  • Population characteristics according to recruitment source.

    abstract::Considerable variability was observed among recruitment sources and centers in the proportion of first protocol visits proceeding to entry. Some of the reasons for these differences are explored. Several characteristics of the participants were also analyzed to determine whether significant variability existed among r...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Hunninghake DB,Knoke J,LaDouceur M,Peterson F

    更新日期:1982-12-01 00:00:00

  • HDLs containing apolipoproteins A-I and A-II (LpA-I:A-II) as markers of coronary artery disease in men with non-insulin-dependent diabetes mellitus.

    abstract:BACKGROUND:Abnormalities in HDL and an increased risk of coronary artery disease (CAD) coexist in non-insulin-dependent diabetes mellitus (NIDDM). HDLs can be separated by their apolipoprotein (apo) content into particles containing apoA-I but not apoA-II (LpA-I) and those containing both apoA-I and apoA-II (LpA-I:A-II...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.92.3.364

    authors: Syvänne M,Kahri J,Virtanen KS,Taskinen MR

    更新日期:1995-08-01 00:00:00

  • Incremental value of the preoperative echocardiogram to predict mortality and major morbidity in coronary artery bypass surgery.

    abstract:BACKGROUND:Although echocardiography is commonly performed before coronary artery bypass surgery, there has yet to be a study examining the incremental prognostic value of a complete echocardiogram. METHODS AND RESULTS:Patients undergoing isolated coronary artery bypass surgery at 2 hospitals were divided into derivat...

    journal_title:Circulation

    pub_type: 杂志文章,多中心研究

    doi:10.1161/CIRCULATIONAHA.112.127639

    authors: Afilalo J,Flynn AW,Shimony A,Rudski LG,Agnihotri AK,Morin JF,Castrillo C,Shahian DM,Picard MH

    更新日期:2013-01-22 00:00:00

  • Association of Baseline and Longitudinal Changes in Body Composition Measures With Risk of Heart Failure and Myocardial Infarction in Type 2 Diabetes: Findings From the Look AHEAD Trial.

    abstract:BACKGROUND:Intentional weight loss is associated with lower risk of heart failure (HF) and atherosclerotic cardiovascular disease among patients with type 2 diabetes. However, the contribution of baseline measures and longitudinal changes in fat mass (FM), lean mass (LM), and waist circumference (WC) to the risk of HF ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.120.050941

    authors: Patel KV,Bahnson JL,Gaussoin SA,Johnson KC,Pi-Sunyer X,White U,Olson KL,Bertoni AG,Kitzman DW,Berry JD,Pandey A,Look AHEAD Research Group.

    更新日期:2020-12-22 00:00:00

  • Selective pharmacological agents implicate mitochondrial but not sarcolemmal K(ATP) channels in ischemic cardioprotection.

    abstract:BACKGROUND:Pharmacological evidence has implicated ATP-sensitive K(+) (K(ATP)) channels as the effectors of cardioprotection, but the relative roles of mitochondrial (mitoK(ATP)) and sarcolemmal (surfaceK(ATP)) channels remain controversial. METHODS AND RESULTS:We examined the effects of the K(ATP) channel blocker HMR...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.101.20.2418

    authors: Sato T,Sasaki N,Seharaseyon J,O'Rourke B,Marbán E

    更新日期:2000-05-23 00:00:00

  • Mortality and Cerebrovascular Events After Heart Rhythm Disorder Management Procedures.

    abstract:BACKGROUND:Recognition of rates and causes of hard, patient-centered outcomes of death and cerebrovascular events (CVEs) after heart rhythm disorder management (HRDM) procedures is an essential step for the development of quality improvement programs in electrophysiology laboratories. Our primary aim was to assess and ...

    journal_title:Circulation

    pub_type: 杂志文章,多中心研究

    doi:10.1161/CIRCULATIONAHA.117.030523

    authors: Lee JZ,Ling J,Diehl NN,Hodge DO,Padmanabhan D,Killu AM,Madhavan M,Noseworthy PA,Kapa S,McLeod CJ,Cha YM,Deshmukh AJ,Srivathsan K,Kusumoto FM,Shen WK,Friedman PA,Munger TM,Asirvatham SJ,Packer DL,Mulpuru SK

    更新日期:2018-01-02 00:00:00

  • 17beta-estradiol antagonizes cardiomyocyte hypertrophy by autocrine/paracrine stimulation of a guanylyl cyclase A receptor-cyclic guanosine monophosphate-dependent protein kinase pathway.

    abstract:BACKGROUND:Significant gender-related differences exist in the development of left ventricular hypertrophy (LVH). In addition, administration of 17beta-estradiol (E2) to ovariectomized female mice attenuates the development of LVH, demonstrating an antagonistic role for E2 in this process, although no molecular mechani...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.CIR.0000105682.85732.BD

    authors: Babiker FA,De Windt LJ,van Eickels M,Thijssen V,Bronsaer RJ,Grohé C,van Bilsen M,Doevendans PA

    更新日期:2004-01-20 00:00:00

  • Chronic aortic regurgitation: reassessment of the prognostic value of preoperative left ventricular end-systolic dimension and fractional shortening.

    abstract::The prognostic significance of a preoperative echocardiographic left ventricular end-systolic dimension (ESD) greater than 55 mm and/or fractional shortening (FS) of 25% or less was evaluated retrospectively in 84 patients who had undergone aortic valve replacement for isolated chronic aortic regurgitation due to vari...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.71.4.669

    authors: Daniel WG,Hood WP Jr,Siart A,Hausmann D,Nellessen U,Oelert H,Lichtlen PR

    更新日期:1985-04-01 00:00:00

  • Valve replacement for aortic stenosis in patients with poor left ventricular function: comparison of early changes with stented and stentless valves.

    abstract:BACKGROUND:Long-standing aortic stenosis causes significant left ventricular (LV) dysfunction, which may progress irreversibly. In many cases, LV function can be salvaged by aortic valve surgery, although debate exists regarding the best valve prosthesis to use. METHODS AND RESULTS:We studied 33 patients retrospective...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.100.suppl_2.ii-1

    authors: Collinson J,Henein M,Flather M,Pepper JR,Gibson DG

    更新日期:1999-11-09 00:00:00

  • Mortality and sudden death in pediatric left ventricular noncompaction in a tertiary referral center.

    abstract:BACKGROUND:Left ventricular noncompaction is a cardiomyopathy characterized by excessive trabeculation of the left ventricle, progressive myocardial dysfunction, and early mortality. Left ventricular noncompaction has a heterogeneous clinical presentation that includes arrhythmia and sudden cardiac death. METHODS AND ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.113.002511

    authors: Brescia ST,Rossano JW,Pignatelli R,Jefferies JL,Price JF,Decker JA,Denfield SW,Dreyer WJ,Smith O,Towbin JA,Kim JJ

    更新日期:2013-06-04 00:00:00

  • Reduction in myocardial infarct size by basic fibroblast growth factor after temporary coronary occlusion in a canine model.

    abstract:BACKGROUND:Basic fibroblast growth factor (bFGF) has been shown to reduce infarct size in canine acute myocardial infarction; however, the mechanism of tissue salvage remains uncertain. We evaluated the effect of bFGF on infarct size in a model of acute infarction in which coronary occlusion was followed by prolonged r...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.94.8.1927

    authors: Horrigan MC,MacIsaac AI,Nicolini FA,Vince DG,Lee P,Ellis SG,Topol EJ

    更新日期:1996-10-15 00:00:00

  • Linking: a dynamic electrophysiologic phenomenon in macroreentry circuits.

    abstract::The term "linking" has been used specifically to describe the mechanism for perpetuation of functional anterograde bundle branch block: namely, repetitive transseptal retrograde concealed penetration by impulses propagating along the contralateral bundle. We present selected examples that demonstrate tht linking-type ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.71.2.254

    authors: Lehmann MH,Denker S,Mahmud R,Addas A,Akhtar M

    更新日期:1985-02-01 00:00:00

  • Hemodynamic findings in 123 patients with acute myocardial infarction on admission.

    abstract::Hemodynamic and clinical evaluations of 123 patients with acute myocardial infarction were performed during the first hour of admission to the hospital. In the 123 patients, the right atrial pressure was less than 10 mm Hg in 49 patients, the right atrial oxygen saturation was less than 70% in 97 patients, the arterio...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.42.4.567

    authors: Ramo BW,Myers N,Wallace AG,Starmer F,Clark DO,Whalen RE

    更新日期:1970-10-01 00:00:00

  • Efficacy and Safety of a Pharmaco-Invasive Strategy With Half-Dose Alteplase Versus Primary Angioplasty in ST-Segment-Elevation Myocardial Infarction: EARLY-MYO Trial (Early Routine Catheterization After Alteplase Fibrinolysis Versus Primary PCI in Acute

    abstract:BACKGROUND:Timely primary percutaneous coronary intervention (PPCI) cannot be offered to all patients with ST-segment-elevation myocardial infarction (STEMI). Pharmaco-invasive (PhI) strategy has been proposed as a valuable alternative for eligible patients with STEMI. We conducted a randomized study to compare the eff...

    journal_title:Circulation

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1161/CIRCULATIONAHA.117.030582

    authors: Pu J,Ding S,Ge H,Han Y,Guo J,Lin R,Su X,Zhang H,Chen L,He B,EARLY-MYO Investigators.

    更新日期:2017-10-17 00:00:00

  • De subitaneis mortibus. XV. Hereditary stenosis of the His bundle in Pug dogs.

    abstract::Syncope and sudden death occurs in certain purebred Pug dogs which have been found to have intermittent sinus pauses and paroxysmal second degree heart block on electrocardiographic (ECG) study. We have established a colony of such dogs to study this problem and here report the results of histological examination of t...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.52.6.1152

    authors: James TN,Robertson BT,Waldo AL,Branch CE

    更新日期:1975-12-01 00:00:00

  • The QT interval throughout the first 6 months of life: a prospective study.

    abstract::A prospective electrocardiographic study was designed to establish baseline values for electrocardiographic measurements, with specific reference to the QT interval during infancy, and to test the "QT hypothesis" for the sudden infant death syndrome (SIDS). In this ongoing study, ECGs are recorded on the fourth day of...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.66.3.496

    authors: Schwartz PJ,Montemerlo M,Facchini M,Salice P,Rosti D,Poggio G,Giorgetti R

    更新日期:1982-09-01 00:00:00