Disruption of endothelial-cell caveolin-1alpha/raft scaffolding during development of monocrotaline-induced pulmonary hypertension.

Abstract:

BACKGROUND:In the monocrotaline (MCT)-treated rat, there is marked stimulation of DNA synthesis and megalocytosis of pulmonary arterial endothelial cells (PAECs) within 3 to 4 days, followed by pulmonary hypertension (PH) 10 to 14 days later. Growing evidence implicates caveolin-1 (cav-1) in plasma membrane rafts as a negative regulator of promitogenic signaling. We have investigated the integrity and function of endothelial cell-selective cav-1alpha/raft signaling in MCT-induced PH. METHODS AND RESULTS:Although PH and right ventricular hypertrophy developed by 2 weeks after MCT, a reduction in cav-1alpha levels in the lung was apparent within 48 hours, declining to approximately 30% by 2 weeks, accompanied by an increase in activation of the promitogenic transcription factor STAT3 (PY-STAT3). Immunofluorescence studies showed a selective loss of cav-1alpha and platelet endothelial cell adhesion molecule-1 in the PAEC layer within 48 hours after MCT but an increase in PY-STAT3. PAECs with cav-1alpha loss displayed high PY-STAT3 and nuclear immunostaining for proliferating cell nuclear antigen (PCNA). Biochemical studies showed a loss of cav-1alpha from the detergent-resistant lipid raft fraction concomitant with hyperactivation of STAT3. Moreover, cultured PAECs treated with MCT-pyrrole for 48 hours developed megalocytosis associated with hypo-oligomerization and reduction of cav-1alpha, hyperactivation of STAT3 and ERK1/2 signaling, and stimulation of DNA synthesis. CONCLUSIONS:MCT-induced disruption of cav-1alpha chaperone and scaffolding function in PAECs likely accounts for diverse alterations in endothelial cell signaling in this model of PH.

journal_name

Circulation

journal_title

Circulation

authors

Mathew R,Huang J,Shah M,Patel K,Gewitz M,Sehgal PB

doi

10.1161/01.CIR.0000141576.39579.23

subject

Has Abstract

pub_date

2004-09-14 00:00:00

pages

1499-506

issue

11

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000141576.39579.23

journal_volume

110

pub_type

杂志文章
  • The effect of acute changes in coronary blood flow on left ventricular end-diastolic wall thickness. An echocardiographic study.

    abstract::The effect of acute alterations in coronary blood flow (CBF) on left ventricular (LV) end-diastolic wall thickness was measured by reflected ultrasound in twelve anesthetized dogs. During five minutes of coronary ligation, wall thickness decreased from a control of 9.0 +/- 0.3 mm to 8.1 +/- 0.3 mm (P less than 0.001);...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.56.4.593

    authors: Gaasch WH,Bernard SA

    更新日期:1977-10-01 00:00:00

  • High-density lipoprotein deficiency and dyslipoproteinemia associated with venous thrombosis in men.

    abstract:BACKGROUND:Although dyslipoproteinemia is associated with arterial atherothrombosis, little is known about plasma lipoproteins in venous thrombosis patients. METHODS AND RESULTS:We determined plasma lipoprotein subclass concentrations using nuclear magnetic resonance spectroscopy and antigenic levels of apolipoprotein...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.104.521344

    authors: Deguchi H,Pecheniuk NM,Elias DJ,Averell PM,Griffin JH

    更新日期:2005-08-09 00:00:00

  • Effects of intensive versus moderate lipid-lowering therapy on myocardial ischemia in older patients with coronary heart disease: results of the Study Assessing Goals in the Elderly (SAGE).

    abstract:BACKGROUND:Clinical trials have demonstrated that, compared with placebo, intensive statin therapy reduces ischemia in patients with acute coronary syndromes and in patients with stable coronary artery disease. However, no studies to date have assessed intensive versus moderate statin therapy in older patients with sta...

    journal_title:Circulation

    pub_type: 杂志文章,随机对照试验

    doi:10.1161/CIRCULATIONAHA.106.654756

    authors: Deedwania P,Stone PH,Bairey Merz CN,Cosin-Aguilar J,Koylan N,Luo D,Ouyang P,Piotrowicz R,Schenck-Gustafsson K,Sellier P,Stein JH,Thompson PL,Tzivoni D

    更新日期:2007-02-13 00:00:00

  • Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function.

    abstract:BACKGROUND:Adults with obesity or type 2 diabetes mellitus (T2DM) are at higher risk for stroke and myocardial infarction. Increased carotid intima-media thickness (cIMT) and stiffness are associated with these adverse outcomes. We compared carotid arteries in youth who were lean, were obese, or had T2DM. METHODS AND ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.108.830380

    authors: Urbina EM,Kimball TR,McCoy CE,Khoury PR,Daniels SR,Dolan LM

    更新日期:2009-06-09 00:00:00

  • Acute occlusion after percutaneous transluminal coronary angioplasty--a new approach.

    abstract::Between July 1980 and November 1982, there were 935 coronary angioplasties attempted at Emory University Hospital. Of these patients, 20 developed acute occlusion. Of these 20, 19 presented within 3 hr of surgery or within 3 hr after stopping a continuous heparin infusion. Five patients required emergency surgery, but...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.68.4.725

    authors: Hollman J,Gruentzig AR,Douglas JS Jr,King SB 3rd,Ischinger T,Meier B

    更新日期:1983-10-01 00:00:00

  • Comparison of ascending aorta versus femoral artery cannulation for acute aortic dissection type A.

    abstract:BACKGROUND:The site of cannulation for repair of ascending aortic dissection remains controversial. We present our experience with ascending aortic cannulation for acute aortic dissection type A. METHODS AND RESULTS:From January 1988 to September 2007, we operated on 242 patients for acute aortic dissection type A. Me...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.108.844480

    authors: Kamiya H,Kallenbach K,Halmer D,Ozsöz M,Ilg K,Lichtenberg A,Karck M

    更新日期:2009-09-15 00:00:00

  • The nitrovasodilators. New ideas about old drugs.

    abstract::The nitrovasodilators are a diverse group of pharmacological agents that produce vascular relaxation by releasing nitric oxide. The mechanisms by which these compounds release nitric oxide vary, depending on their chemical structure. Compounds with lower oxidation states of nitrogen such as nitroprusside, nitrosamines...

    journal_title:Circulation

    pub_type: 杂志文章,评审

    doi:10.1161/01.cir.87.5.1461

    authors: Harrison DG,Bates JN

    更新日期:1993-05-01 00:00:00

  • Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.

    abstract:BACKGROUND:The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore,...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1161/01.cir.101.9.955

    authors: Doucet S,Malekianpour M,Théroux P,Bilodeau L,Côté G,de Guise P,Dupuis J,Joyal M,Gosselin G,Tanguay JF,Juneau M,Harel F,Nattel S,Tardif JC,Lespérance J

    更新日期:2000-03-07 00:00:00

  • Effect of the ouabain-quinidine interaction on left ventricular and left atrial function in conscious dogs.

    abstract::The effect of the ouabain-quinidine interaction was examined in 10 conscious dogs. Left ventricular (LV) pressure, LV dP/dt, LV diameter and left atrial (LA) diameter were measured with high-fidelity micromanometers and sonomicrometer crystals. Ouabain, 0.025 mg/kg, significantly (p less than 0.05) increased LV dP/dt,...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.67.5.1054

    authors: Goldman S,Hager WD,Olajos M,Perrier D,Mayersohn M

    更新日期:1983-05-01 00:00:00

  • Protection of endothelium in vessel segments excised for grafting.

    abstract::Contracture and collapse often complicate dissection and excision of blood vessels for grafting. Subsequent forceful redilatation and leak checking with cold saline almost always lead to partial or total denudation of endothelium, which increases the risk of early occlusion by thrombi or late occlusion by fibrocellula...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Haudenschild C,Gould KE,Quist WC,LoGerfo FW

    更新日期:1981-08-01 00:00:00

  • Ibutilide, a methanesulfonanilide antiarrhythmic, is a potent blocker of the rapidly activating delayed rectifier K+ current (IKr) in AT-1 cells. Concentration-, time-, voltage-, and use-dependent effects.

    abstract:BACKGROUND:Ibutilide is an action potential-prolonging antiarrhythmic currently in clinical trials. The drug shares structural similarities with E-4031 and dofetilide, specific blockers of the rapidly activating delayed rectifier K+ current (IKr). However, previous in vitro studies in guinea pig myocytes have indicated...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.91.6.1799

    authors: Yang T,Snyders DJ,Roden DM

    更新日期:1995-03-15 00:00:00

  • Endocardial catheter mapping: wire skeleton technique for representation of computed arrhythmogenic sites compared with intraoperative mapping.

    abstract::Guiding surgical therapy of ventricular tachycardia by preoperative endocardial catheter mapping necessitates improvement of the accuracy of localization of the arrhythmogenic site. We therefore used a new mathematical cineradiographic method during catheter mapping to compute the position of left ventricular arrhythm...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.74.6.1346

    authors: Hauer RN,de Zwart MT,de Bakker JM,Hitchcock JF,Penn OC,Nijsen-Karelse M,Robles de Medina EO

    更新日期:1986-12-01 00:00:00

  • Left ventricular function in trained and untrained healthy subjects.

    abstract::Left ventricular function was compared in 18 normal sedentary controls (mean age 28 years, range 22 - 34 years) and nine endurance-trained athletes (mean age 19 years, range 15 - 25 years) at rest and during supine bicycle exercise. Gated radionuclide angiocardiograms were performed at rest and at each level of graded...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.65.3.484

    authors: Bar-Shlomo BZ,Druck MN,Morch JE,Jablonsky G,Hilton JD,Feiglin DH,McLaughlin PR

    更新日期:1982-03-01 00:00:00

  • Endogenous nitric oxide synthase inhibitor: a novel marker of atherosclerosis.

    abstract:BACKGROUND:Exposure to risk factors such as hypertension or hypercholesterolemia decreases the bioavailability of endothelium-derived nitric oxide (NO) and impairs endothelium-dependent vasodilation. Recently, a circulating endogenous NO synthase inhibitor, asymmetric dimethylarginine (ADMA), has been detected in human...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.99.9.1141

    authors: Miyazaki H,Matsuoka H,Cooke JP,Usui M,Ueda S,Okuda S,Imaizumi T

    更新日期:1999-03-09 00:00:00

  • Acute effect of intravenous dipyridamole on regional coronary hemodynamics and metabolism.

    abstract::The acute coronary hemodynamic and metabolic effects of intravenous dipyridamole were studied in 13 patients. Total left ventricular (LV), anterior (supplied by the left anterior descending coronary artery) and inferior (supplied by circumflex and right coronary arteries) regional flows and metabolic responses were as...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.64.2.333

    authors: Feldman RL,Nichols WW,Pepine CJ,Conti CR

    更新日期:1981-08-01 00:00:00

  • Body-surface maps of heart potentials: tentative localization of pre-excited areas in forty-two Wolff-Parkinson-White patients.

    abstract::Heart potentials were recorded from the entire chest surface in 42 patients suffering from Wolff-Parkinson-White syndrome. We were able to identify six types of surface maps, according to the location of the potential maximum and minimum during the delta wave. For each of these types we suggested the most likely locat...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.54.2.251

    authors: De Ambroggi L,Taccardi B,Macchi E

    更新日期:1976-08-01 00:00:00

  • Outcome of the Fontan procedure in patients with tricuspid atresia.

    abstract::Between 1973 and 1983, 90 patients with tricuspid atresia underwent the Fontan operation at the Mayo Clinic. Operative mortality was 12% overall and decreased to 7% during the second 5 year period. At postoperative follow-up of 65 patients (1 to 10 years, mean 4), 50 (86%) of 58 present survivors were in excellent con...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:

    authors: Mair DD,Rice MJ,Hagler DJ,Puga FJ,McGoon DC,Danielson GK

    更新日期:1985-09-01 00:00:00

  • Mitral leaflet adaptation to ventricular remodeling: occurrence and adequacy in patients with functional mitral regurgitation.

    abstract:BACKGROUND:Functional mitral regurgitation (MR) is caused by systolic traction on the mitral leaflets related to ventricular distortion. Little is known about whether chronic tethering causes the mitral leaflet area to adapt to the geometric needs imposed by tethering, in part because of inability to reconstruct leafle...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.107.749440

    authors: Chaput M,Handschumacher MD,Tournoux F,Hua L,Guerrero JL,Vlahakes GJ,Levine RA

    更新日期:2008-08-19 00:00:00

  • Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus.

    abstract:BACKGROUND:Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subje...

    journal_title:Circulation

    pub_type: 临床试验,杂志文章

    doi:10.1161/01.cir.0000036596.59665.c6

    authors: Diamant M,Nieuwland R,Pablo RF,Sturk A,Smit JW,Radder JK

    更新日期:2002-11-05 00:00:00

  • Coronary angioplasty of multiple vessels: short-term outcome and long-term results.

    abstract::Experience with percutaneous transluminal coronary angioplasty (PTCA) of multiple vessels was reviewed to assess short-term outcome and long-term results. PTCA of multiple vessels was performed in 100 of the initial 500 patients (20%) who underwent PTCA at the Medical College of Virginia between July 1979 and August 1...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.72.6.1314

    authors: Cowley MJ,Vetrovec GW,DiSciascio G,Lewis SA,Hirsh PD,Wolfgang TC

    更新日期:1985-12-01 00:00:00

  • Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance.

    abstract:BACKGROUND:The cardiovascular adaptation to bed rest leads to orthostatic intolerance, characterized by an excessive fall in stroke volume (SV) in the upright position. We hypothesized that this large fall in SV is due to a change in cardiac mechanics. METHODS AND RESULTS:We measured pulmonary capillary wedge pressure...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.96.2.517

    authors: Levine BD,Zuckerman JH,Pawelczyk JA

    更新日期:1997-07-15 00:00:00

  • Intrapericardial paclitaxel delivery inhibits neointimal proliferation and promotes arterial enlargement after porcine coronary overstretch.

    abstract:BACKGROUND:Catheter-based intrapericardial (IPC) delivery of therapeutic agents has recently been demonstrated. Paclitaxel is known to inhibit vascular smooth muscle cell proliferation. This study examined the effect of IPC instillation of paclitaxel on neointimal proliferation after balloon overstretch of porcine coro...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.102.13.1575

    authors: Hou D,Rogers PI,Toleikis PM,Hunter W,March KL

    更新日期:2000-09-26 00:00:00

  • A randomized trial of recombinant staphylokinase versus alteplase for coronary artery patency in acute myocardial infarction. The STAR Trial Group.

    abstract:BACKGROUND:Recombinant staphylokinase (STAR) was shown recently to offer promise for coronary arterial thrombolysis in patients with evolving myocardial infarction. The present multicenter randomized open trial was designed to assess the thrombolytic efficacy, safety, and fibrin specificity of STAR relative to accelera...

    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.92.8.2044

    authors: Vanderschueren S,Barrios L,Kerdsinchai P,Van den Heuvel P,Hermans L,Vrolix M,De Man F,Benit E,Muyldermans L,Collen D

    更新日期:1995-10-15 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

  • Targeted deletion of Fgl-2/fibroleukin in the donor modulates immunologic response and acute vascular rejection in cardiac xenografts.

    abstract:BACKGROUND:Xenografts ultimately fail as a result of acute vascular rejection (AVR), a process characterized by intravascular thrombosis, fibrin deposition, and endothelial cell activation. METHODS AND RESULTS:We studied whether targeted deletion of Fgl-2, an inducible endothelial cell procoagulant, (Fgl-2-/-) in the ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.105.534271

    authors: Mendicino M,Liu M,Ghanekar A,He W,Koscik C,Shalev I,Javadi M,Turnbull J,Chen W,Fung L,Sakamoto S,Marsden P,Waddell TK,Phillips MJ,Gorczynski R,Levy GA,Grant D

    更新日期:2005-07-12 00:00:00

  • Differential cardiac effects of growth hormone and insulin-like growth factor-1 in the rat. A combined in vivo and in vitro evaluation.

    abstract:BACKGROUND:Despite their increasing clinical use and recent evidence that growth hormone (GH) and insulin-like growth factor-1 (IGF-1) target the heart, there has been no systematic investigation of the effects of GH and IGF-1 on the cardiovascular system. METHODS AND RESULTS:Sixty normal but growing adult female rats...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.93.4.800

    authors: Cittadini A,Strömer H,Katz SE,Clark R,Moses AC,Morgan JP,Douglas PS

    更新日期:1996-02-15 00:00:00

  • Endothelial nitric oxide production and insulin sensitivity. A physiological link with implications for pathogenesis of cardiovascular disease.

    abstract:BACKGROUND:Insulin sensitivity varies up to threefold in apparently healthy individuals, but the mechanism for this is unknown. We have examined the hypothesis that vascular endothelial nitric oxide production and insulin sensitivity are directly related in humans. METHODS AND RESULTS:Nineteen healthy male subjects we...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.93.7.1331

    authors: Petrie JR,Ueda S,Webb DJ,Elliott HL,Connell JM

    更新日期:1996-04-01 00:00:00

  • Cardiac specific creatine phosphokinase isoenzyme in the diagnosis of acute myocardial infarction.

    abstract::The specific and sensitivity of serum creatine phosphokinase cardiac specific isoenzyme (MB) in the diagnosis of acute myocardial infarction (AMI) was evaluated. An ion-exchange chromatographic technique was used to isolate MB. Sera layered on mini-columns of DEAE-Sephadex were eluted with Tris-buffered sodium chlorid...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/01.cir.51.5.855

    authors: Varat MA,Mercer DW

    更新日期:1975-05-01 00:00:00

  • Increased mortality, postoperative morbidity, and cost after red blood cell transfusion in patients having cardiac surgery.

    abstract:BACKGROUND:Red blood cell transfusion can both benefit and harm. To inform decisions about transfusion, we aimed to quantify associations of transfusion with clinical outcomes and cost in patients having cardiac surgery. METHODS AND RESULTS:Clinical, hematology, and blood transfusion databases were linked with the UK ...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.107.698977

    authors: Murphy GJ,Reeves BC,Rogers CA,Rizvi SI,Culliford L,Angelini GD

    更新日期:2007-11-27 00:00:00

  • Visceral adipose tissue inflammation accelerates atherosclerosis in apolipoprotein E-deficient mice.

    abstract:BACKGROUND:Fat inflammation may play an important role in comorbidities associated with obesity such as atherosclerosis. METHODS AND RESULTS:To first establish feasibility of fat transplantation, epididymal fat pads were harvested from wild-type C57BL/6J mice and transplanted into leptin-deficient (Lep(ob/ob)) mice. F...

    journal_title:Circulation

    pub_type: 杂志文章

    doi:10.1161/CIRCULATIONAHA.107.717595

    authors: Ohman MK,Shen Y,Obimba CI,Wright AP,Warnock M,Lawrence DA,Eitzman DT

    更新日期:2008-02-12 00:00:00