Imatinib Mesylate Has The Potential to Exert Its Efficacy by Down-Regulating The Plasma Concentration of Platelet-Derived Growth Factor in Patients With Pulmonary Arterial Hypertension
スポンサーリンク
概要
- 論文の詳細を見る
Recently, platelet-derived growth factor (PDGF) has been implicated in the abnormal proliferation and migration of pulmonary artery vascular smooth muscle cells. Imatinib meslylate, a PDGF receptor antagonist, has been reported to dramatically improve pulmonary arterial hypertension (PAH) in some human cases as well as animal models.Five patients with PAH (3 scleroderma-associated PAH and 2 idiopathic/familial PAH) taking no less than 2 PAH agents were treated with low-dose imatinib (100 mg/day) for 24 weeks. Imatinib was titrated up to 200 mg/day unless major complications were observed. Before and after the treatment, right heart catheterization, cardiopulmonary exercise test, respiratory function test, and plasma concentration measurements of PDGF-BB and vascular endothelial growth factor (VEGF) were performed. Plasma PDGF-BB levels were significantly decreased after 12 weeks of treatment (P = 0.04), while VEGF did not change. Although 24 week administration of imatinib did not show a significant effect on hemodynamics and exercise capacity, 2 patients with high plasma PDGF-BB levels showed a good initial response of more than a 15% decrease in pulmonary vascular resistance. Diffusion capacity of the lung for carbon monoxide significantly improved after 12 weeks of treatment (P < 0.01) and this improvement tended to be sustained for 24 weeks (P = 0.05). Renal dysfunction was observed in 3 patients during imatinib therapy.The upregulated PDGF-BB in patients with PAH could be suppressed by imatinib treatment, and also seemed to be one of the determinant factors for its efficacy.
著者
-
Hirata Yasunobu
Department Of Advanced Clinical Science And Therapeutics Cardiovascular Medicine Graduate School Of
-
Shiga Taro
Department Of Cardiovascular Medicine Graduate School Of Medicine The University Of Tokyo
-
Hatano Masaru
Department Of Cardiology Narita Red Cross Hospital
-
Kinugawa Koichiro
Department Of Cardiovascular Medicine Graduate School Of Medicine University Of Tokyo
-
Yao Atsushi
Department Of Cardiology Tokyo University Hospital
-
Nagai Ryozo
Department Cardiovascular Medicine The University Of Tokyo Hospital
-
Kinugawa Koichiro
Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo
関連論文
- PJ-369 Adipose Tissue-Derived Cells Inhibit Neointimal Formation in a Paracrine Fashion via Stimulation of Reendothelialization(PJ062,Regeneration (Basic, Clinical) (M),Poster Session (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulati
- Blockade of Endogenous Proinflammatory Cytokines Ameliorates Endothelial Dysfunction in Obese Zucker Rats
- PJ-410 Angiotensinll and Tumor Necrosis Factor-α Cooperatively Stimulate MCP-1 Expression via Utilization of Distinct Intracellular Signaling p38- and NFkB-dependent Pathways(Atherosclerosis, basic(07)(IHD),Poster Session(Japanese),The 72nd Annual Scienti
- A Case of Neonatal Lupus Erythematosus Presenting Delayed Dilated Cardiomyopathy With Circulating Autoantibody to Annexin A6
- PE-145 The Clinical Application of the Pharmacogenomics for Optimizing Warfarin Dosage(PE025,Thromboembolism/Antithrombotic Therapy/Thrombolysis 2 (IHD),Poster Session (English),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
- The Matrix Metalloproteinase-1 (MMP-1) 1G/2G Polymorphism and the Matrix Metalloproteinase-3 (MMP-3) 5A/6A Polymorphism are Useful Genetic Markers for Myocardial Infarction
- Successful Catheter Intervention for Acute Coronary Syndrome in a Patient with Antiphospholipid Syndrome
- PE-267 Impact of Smoking and HDL-C on Coronary Plaque Regression during Statin Therapy in Acute Coronary Syndrome (ACS) : Sub-analysis of JAPAN-ACS(PE045,ACS/AMI (Clinical/Treatment) 2 (IHD),Poster Session (English),The 73rd Annual Scientific Meeting of T
- Relationship Between Renal Dysfunction and Severity of Coronary Artery Disease in Japanese Patients
- PJ-038 Cystatin C Predicts Severity of Coronary Artery Disease Even in Patients without Chronic Kidney Disease (CKD)(PJ007,Kidney/Renal Circulation/CKD 1 (H),Poster Session (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
- PJ-594 Clinical Impact of Intravascular Ultrasound-guided Renal Artery Stenting Using Low-Profile Stent System (Parmaz-Genesis) for Treatment of Renal Artery Stenosis(PJ100,Kidney/Renal Circulation/CKD 5 (H),Poster Session (Japanese),The 73rd Annual Scien
- OE-044 Long Pentraxin 3 (PTX3) is More Specific than C-reactive Protein (CRP) as a Marker for Vascular Inflammation(Atherosclerosis, clinical-01, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- OE-236 Genetic Deletion of Angiotensin-converting Enzyme 2 Exacerbates Neointimal Hyperplasia after Wire-mediated Endovascular Injury with Regional Severe Inflammation(OE40,Atherosclerosis, Basic 2 (IHD),Oral Presentation (English),The 73rd Annual Scienti
- Carvedilol Therapy Improved Left Ventricular Function in a Patient With Arrhythmogenic Right Ventricular Cardiomyopathy
- Class of Antihypertensive Drugs, Blood Pressure Status, and Risk of Cardiovascular Disease in Hypertensive Patients : A Case-Control Study in Japan
- Three-vessel Coronary Artery Disease Complicated with Congestive Heart Failure in a Highly Aged Patient with Tetralogy of Fallot Having Undergone Palliative Surgeries
- Hematopoietic stem cells differentiate into vascular progenitor cells that contribute to atherosclerosis
- Hypertrophic Cardiomyopathy With Midventricular Obstruction and Apical Aneurysm : A Case Report
- PE-513 Three Dimensional Echocardiography Provides New Indexes for the Evaluation of Pulmonary Hypertension(PE086,Pulmonary Circulation (H),Poster Session (English),The 73rd Annual Scientific Meeting of the Japanese Circulation Society)
- PE-505 Resistance Training Combined with Aerobic One Effectively Improves Exercise Capacity in Patients Implanted with TOYOBO LVAS(PE085,Exercise Test/Cardiac Rehabilitation (H),Poster Session (English),The 73rd Annual Scientific Meeting of the Japanese C
- PE-244 Less Frequency of Native Aortic Valve Opening Causes Aortic Regurgitation in Patients with Left Ventricular Assist Device (LVAD)(PE041,Transplantation/LVAD (M),Poster Session (English),The 73rd Annual Scientific Meeting of The Japanese Circulation
- PE-241 Preoperative Clinical Profiles Predict Prognosis after Left Ventricular Assist Device Implantation(PE041,Transplantation/LVAD (M),Poster Session (English),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
- Takayasu Myocarditis Mediated by Cytotoxic T Lymphocytes
- Enhancement of Endothelial Nitric Oxide Production by Chenodeoxycholic Acids in Patients with Hepatobiliary Diseases
- In early-stage diabetic retinopathy, risk of cardiac events after implantation of sirolimus-eluting stent is higher than after coronary artery bypass surgery
- OE-177 A series of Cardiopulmonary Exercise Test for LVAS patients, Which is Combined with Pump Off-tests, Effectively Predicts Device Explantability(Exercise test/Cardiac rehabilitation(01)(H),Oral Presentation(English),The 72nd Annual Scientific Meeting
- OJ-188 Cardiac Rehabilitation Improves Plasma Pentraxin3 Level in Patients with Cardiovascular Disease(OJ32,Exercise Test/Cardiac Rehabilitation (H),Oral Presentation (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
- OE-336 Cardiac Rehabilitation for LVAS Patients and the Estimation of the Possibility of LVAS Explantation Using Cardiopulmonary Exercise Test(Exercise test/Cardiac rehabilitation-1, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- OE-335 Effect of Peak and Endurance Exercises on the Number of Circulating Endothelial Progenitor Cells (EPCs)(Exercise test/Cardiac rehabilitation-1, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- PJ-759 Hemodynamic and Autonomic Nervous Responses to the Restriction of Femoral Blood Flow by Kaatsu(Exercise test/Cardiac rehabilitation-6 (IHD) PJ131,Poster Session (Japanese),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation S
- PJ-188 Hemodynamic and Hormonal Responses to Short-Term Low-Resistance Exercise with Restricted Muscle Blood Flow(Exercise Test/Cardiac Rehabilitation 2 (IHD) : PJ32)(Poster Session (Japanese))
- Imatinib Mesylate Has The Potential to Exert Its Efficacy by Down-Regulating The Plasma Concentration of Platelet-Derived Growth Factor in Patients With Pulmonary Arterial Hypertension
- Candesartan Ameliorates Cardiac Dysfunction Observed in Angiotensin-Converting Enzyme 2-Deficient Mice
- Endothelial Responses of the Aorta from Adrenomedullin Transgenic Mice and Knockout Mice
- Accelerated Cardiac Hypertrophy and Renal Damage Induced by Angiotensin II in Adrenomedullin Knockout Mice
- PE-427 Blockade of Angiotensin II Type 1 Receptor Attenuates the Post-Infarcted Cardiac Dysfunction in Angiotensin-converting Enzyme 2 Deficient Mice(Heart failure, basic-3, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- OE-104 A Synthetic Prostaglandin I2 Agonist Up-regulates Endogenous Growth Factors Via c-AMP Mediated Pathway and Promotes Therapeutic Angiogenesis(Growth factor/Cytokine-1(H/M), The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- 2 Diverse Contribution of Bone Marrow-derived Cells to Vascular Remodeling Assoclated with Pulmonary Arterial Hypertension and Arterial Neointimal Formation(The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- OE-129 Targeted Disruption of Angiotensin-converting Enzyme 2 Deteriorates Cardiac Performance(Heart failure, basic-1 (M) OE22,Oral Presentation (English),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Society)
- Adipose Tissues Contain Side Population (SP) Cells(Apoptosis/Necrosis/Regeneration 3 (M), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Local Delivery of Slow-releasing Synthetic Prostaglandin I_2 Agonist Augments Collateral Growth in Swine Chronic Cardiac Ischemia Model
- Direct Injection of Synthetic Prostaglandin 12 Agonist Stimulates Expression of Endogenous Growth Factors and Inhibits Cardiac Remodeling after Myocardial Infarction(Acute Myocardial Infarction, Basic 4 (IHD), The 69th Annual Scientific Meeting of the Jap
- Targeted Disruption of Angiotensin-converting Enzyme 2 Results in Spontaneous Heart Failure(Heart Failure, Basic 1 (M), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- PE-562 Reconstituted High-Density Lipoprotein Promotes Differentiation of Endothelial Progenitor Cells and Augments Ischemia-induced Angiogenesis(Regeneration (angiogenesis/myocardial regeneration)-3, The 71st Annual Scientific Meeting of the Japanese Cir
- Significance of B-Type Natriuretic Peptide Measurement in Patients With Chronic Kidney Disease
- Photocatalytic Activity of Titanium Dioxide Loaded with Cerium Oxide
- Effects of Vasodilatory Antihypertensive Agents on Endothelial Dysfunction in Rats with Ischemic Acute Renal Failure
- The role of AMP-activated protein kinase in the cardiovascular system
- PE-573 Phosphodiesterase-5 Inhibition and cGMP Promote Ischemia-induced Angiogenesis through Inducing Vascular Endothelial Growth Factor Production via the Hypoxia Inducible Factor-1 Pathway(Regeneration(angiogenesis/myocardial regeneration)(03)(M),Poster
- PE-153 Acceleration of Hyperlipidemia-induced Atherosclerosis in Angiotensin-converting Enzyme 2 and Apolipoprotein E Double-mutant Mice(Atherosclerosis, basic(04)(IHD),Poster Session(English),The 72nd Annual Scientific Meeting of the Japanese Circulation
- 1 Genetic Deletion of Angiotensin-converting Enzyme 2 Accelerates Hyperlipidemia-induced Atherosclerosis in Apolipoprotein E-deficient Mice(Plenary Session 3 (PL-3) (IHD) Roles of Inflammation and Immunity in Atherosclerosis,Special Program,The 72nd Annua
- OE-322 A Combination of a Cyclic GMP-specific Phosphodiesterase-5 Inhibitor, Vardenafil, and Nicorandil Ameliorates Synergistically Monocrotaline-induced Pulmonary Arterial Hypertension in Rats(Pulmonary circulation-1, The 71st Annual Scientific Meeting o
- FRS-059 cGMP-specific Phosphodiesterase-5 Inhibition Enhances Angiogenesis via the Synthesis of Vascular Endothelial Growth Factor and the Recruitment of Endothelial Progenitor Cells(Regeneration, The 71st Annual Scientific Meeting of the Japanese Circula
- 3 Nicorandil Attenuates Monocrotaline-induced Pulmonary Arterial Hypertension in Rats : The Promising Therapeutic Potential of a Novel Combination Therapy(Diagnosis and Treatment of Pulmonary Hypertension, The 71st Annual Scientific Meeting of the Japanes
- PE-620 Diverse Contribution of Bone Marrow-derived Cells to Vascular Remodeling between Carotid Arteries Injured Mechanically and Pulmonary Vasculature Injured by Monocrotaline(Regeneration (angionenesis/myocardial regeneration)-6 (M) PE110,Poster Session
- PE-277 The Potential Therapeutic Efficacy of Cyclic GMP-specific Phosphodiesterase-5 Inhibition for Angiogenesis in a Mouse Hindlimb Ischemia Model(Peripheral circulation-5 (H) PE47,Poster Session (English),The 70th Anniversary Annual Scientific Meeting o
- OJ-191 A Silk-based Biodegradable Artificial Blood Vessel for Small Artery(Cardiovascular surgery/CABG-1 (IHD) OJ32,Oral Presentation (Japanese),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Society)
- A Highly Purified Hematopoietic Stem Cell Does Not Substantially Contribute to Vascular Remodeling after Mechanical Injury(Development and Differentiation 1 (M), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Bone Marrow-derived Cells Do Not Contribute Appreciably to the Pulmonary Arterial Remodeling in Rats with Monocrotaline-induced Pulmonary Hypertension(Pulmonary Circulation 3 (H), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Insulin Receptor Substrate Deficient Mice Demonstrates Elevated Blood Pressure and Endothelial Cell Dysfunction
- Relationship Between Renal Dysfunction and Severity of Coronary Artery Disease in Japanese Patients : Reply
- PJ-101 Endogenous Angiotensin II and Tumor Necrosis Factor-α Cooperatively Promote Neointimal Formation in the Injured Artery(Molecular biology, vascular-3 (H) PJ17,Poster Session (Japanese),The 70th Anniversary Annual Scientific Meeting of the Japanese C
- Tumor Necrosis Factor-α Enhances Angiotensin II-Induced Reseactive Oxygen Species Production in Vascular Myocytes (Atherosclerosis, Basic 7 (IHD), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Blockade of Endogenous Tumor Necrosis Factor-α Mitigates the Neointimal Formation in Obese Zucker Rats(Diabetes/Obesity 8 (H), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- OJ-515 AMP-activated Protein Kinase Inhibits Angiotensin II-stimulated Vascular Smooth Muscle Cells Proliferation(Vascular Smooth Muscle 2 (H) : OJ63)(Oral Presentation (Japanese))
- FRS-014 Adremedullin augments collateral development and mobilization of endothelial progenitor cells (EPCs) in response to acute ischemia(Angiogenesis and Regeneration Medicine in Cardiovascular Medicine (M) : FRS3)(Featured Research Session (English))
- OJ-056 Augmented Angiogenesis in Adventitia Promotes Plaque Progression in Apolipoprotein E-deficient Mice(OJ10,Atherosclerosis, Basic (IHD),Oral Presentation (Japanese),The 73rd Annual Scientific Meeting of The Japanese Circulation Society)
- Constitutive Activation of Proto-Oncogen Protein p21 Induces Cell Cycle Arrest in the G1 Phase in Contact-Inhibited Vascular Endothelial Cells
- Primitive Stem Cell and Its Pathogenesis of Intracoronary Thrombi in ACS Patients(Thrombosis/Thrombolysis 3 (IHD), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Temporal Analysis of Cellular Constituents of Intracoronary Thrombi in ACS Patients Aspirated Through Thrombectomy(Acute Coronary Syndrome, Basic/Clinical 4 (IHD), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Protective effect of adrenomedullin against cardiac hypertrophy and renal damage
- A new constitutively active mutant of AMP-activated protein kinase inhibits anoxia-induced apoptosis of vascular endothelial cell
- PJ-755 The Heme Oxygenase-Carbon Monoxide Pathway Protects against Hypoxia-Induced Cell Death of Bovine Endothelial Cells through Suppression of NAD(P)H Oxidases(Endothelium-6 (H) PJ130,Poster Session (Japanese),The 70th Anniversary Annual Scientific Meet
- Adrenomedullin Reduction Enhances Hypertrophic Response and Dysfunction of the Heart : Studies on AM Knockout Mice
- Plasma Cystatin C Concentration Reflects the Severity of Coronary Artery Disease in Patients Without Chronic Kidney Disease
- PE-035 Perivascular Adipose Tissues Anatomically Communicate with Atherosclerotic Lesions via Vasa Vasorum : Possible Link of Adipovascular Axis(Atherosclerosis, basic-4, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- PJ-629 Perivascular Fats Anatomically Communicate with Atherosclerotic Lesions via Vasa Vasorum; Possible Link of Adipo-vascular Axis(Atherosclerosis, basic-6 (H) PJ106,Poster Session (Japanese),The 70th Anniversary Annual Scientific Meeting of the Japane
- PE-158 Circulating Progenitors Contribute to Neointimal Formation in Non-irradiated Bone Marrow Chimeric Mice(Atherosclerosis, basic-4 (H) PE27,Poster Session (English),The 70th Anniversary Annual Scientific Meeting of the Japanese Circulation Society)
- Circulating Progenitors Contribute to Neointimal Formation in Non-irradiated Bone Marrow Chimeric Mice(Atherosclerosis, Basic 1 (IHD), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Gene Transfer of Adrenomedullin Augments Collateral Development in Response to Acute Ischemia
- Contribution of Bone Marrow Derived Smooth Muscle Progenitor Cells in the Pathogenesis of Aortic Aneurysm Formation Induced by Angiotensin II(The Frontier of Atherosclerosis Research (IHD), The 69th Annual Scientific Meeting of the Japanese Circulation So
- OJ-299 Potent Inhibitory Effects of Sirolimus on Circulating Smooth Muscle Progenitor Cells(Restenosis after Angioplasty, Basic/Clinical 2 (IHD) : OJ36)(Oral Presentation (Japanese))
- OJ-065 Statins Inhibit Differentiation of Smooth Muscle Progenitor Cells(Lipid Disorders 1 (H) : OJ8)(Oral Presentation (Japanese))
- OE-163 Genetic visualization of differentiation in living cells : Potential applications of a transgenic mouse that expresses EGFP in smooth muscle(Restenosis after Angioplasty, Basic/Clinical 1 (IHD) : OE20)(Oral Presentation (English))
- FRS-124 Hyperlipidemia Increases the Number of Circulating Smooth Muscle Progenitor Cells(Metabolic Syndrome (H) : FRS15)(Featured Research Session (English))
- 7 Potent Inhibitory Effects of Sirolimus on Circulating Smooth Muscle Progenitor Cells(Plenary Session 4 (PL4) (IHD) : Restenosis after PCI 2003 : New Therapies for the Next Generation)(Special Program)
- Familial Atrial Septal Defect and Atrioventricular Conduction Disturbance Associated With a Point Mutation in the Cardiac Homeobox Gene CSX/NKX2-5 in a Japanese Patient
- OJ-334 Bone Marrow Derived Progenitor Cells Participate in the Pathogenesis of Degenerative Valvular Remodeling(Valvular Heart Disease/Pericarditis/Cardiac Tumor 2 (M) : OJ40)(Oral Presentation (Japanese))
- OE-122 Diverse Contribution of Bone Marrow Cells to Vascular Remodeling after Mechanical Injuries(Atherosclerosis, Basic 1 (IHD) : OE14)(Oral Presentation (English))
- Bone Marrow Derived Progenitor Cells Contribute to Progression and Destabilization of Advanced Atherosclerotic Plaques
- Severe Injury Recruits Bone Marrow Derived Progenitor Cells to Vascular Remodeling
- OJ-263 AMP-activated Protein Kinase Signaling in Skeletal Muscle Cells Is Essential for Angiogenesis in Response to Hypoxic Stress(Angiogenesis 2 (M) : OJ31)(Oral Presentation (Japanese))
- A critical role of sympathetic nerve regulation for the treatment of impaired daily rhythm in hypertensive Dahl rats
- Age and Preoperative Total Bilirubin Level Can Stratify Prognosis After Extracorporeal Pulsatile Left Ventricular Assist Device Implantation
- Acute Effect of Sildenafil Is Maintained in Pulmonary Arterial Hypertension Patients Chronically Treated With Bosentan
- Successful Blood Sampling Through Azygos Continuation With Interrupted Inferior Vena Cava : A Case Report and Review of the Literature
- Less Frequent Opening of the Aortic Valve and a Continuous Flow Pump Are Risk Factors for Postoperative Onset of Aortic Insufficiency in Patients With a Left Ventricular Assist Device
- Endothelial Progenitor Cells Contribute Collateral Development by Adrenomedullin(Vasoactive Compound/Growth Factor/Cytokine 1 (H), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Quality of Life as an Independent Predictor for Cardiac Events and Death in Patients With Heart Failure
- FRS-094 Bone Marrow Derived Progenitor Cells Participate in Remodeling of Advanced Atherosclerotic Plaques(Inflammation and Cardiovascular Disease (IHD) : FRS12)(Featured Research Session (English))