Study for Molecular mechanism of cardiorenal connection.

2010 Fiscal Year Final Research Report

• Project/Area Number: 20390227
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Nara Medical University
• Principal Investigator: SAITO Yoshihiko Nara Medical University, 医学部, 教授 (30250260)
• Project Period (FY): 2008 – 2010
• Keywords: 心腎連関 / 腎不全 / 心不全 / sFlt / Klotho

Research Abstract

Many clinical findings proves the close interaction of the heart and kidney diseases, but its molecular mechanism is not fully understood. Here we show, that the circulating plasma level of soluble Flt-1 is reduced in renal dysfunction and that PlGF/Flt-1 system is relatively activated in renal dysfunction, leading the worsening of atherosclerosis. We also find Klotho mRNA expression is reduced in the distal tubules in diabetic nephropaty and raise possibility of Klotho is involved in hypercalciuria and thereby atherosclerosis in renal dysfunction.

Research Products

• [Journal Article] Roles of Guanylyl Cyclase-A Signaling in Cardiovascular System. (2011)
  • Author(s): Saito Y, Kishimoto I, Nakao K
  • Journal Title: Canadian J Physiology and Pharmacology in press
• [Journal Article] for the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators. Differential Effect of Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Diabetic Management : A Subanalysis of the JPAD Trial. (2011)
  • Author(s): Okada S, Morimoto T, Ogawa H, Kanauchi M, Nakayama M, Uemura S, Doi N, Jinnouchi H, Waki M, Soejima H, Sakuma M, Saito Y
  • Journal Title: Diabetes Care. in press
• [Journal Article] Rare Concurrence of Apical Hypertrophic Cardiomyopathy and Effusive Constrictive Pericarditis. (2011)
  • Author(s): Okayama S, Soeda T, Seno A, Watanabe M, Nakajima T, Uemura S, Saito Y
  • Journal Title: The Open Cardiovascular Medicine Journal. in press
• [Journal Article] Myocardial hypoperfusion detected by cardiac computed tomography in an adult patient with heart failure after classic repair for corrected transposition of the great arteries. (2011)
  • Author(s): Okayama S, Seno A, Soeda T, Takami Y, Horii M, Uemura S, Saito Y
  • Journal Title: Acta Cardiologica. in press
• [Journal Article] Atrial right-to-left shunt without pulmonary hypertension in a patient with biventricular non-compaction cardiomyopathy accompanied by ventricular and atrial septal defects. (2011)
  • Author(s): Sakan H, Okayama S, Uemura S, Somekawa S, Ishigami K, Takeda Y, Kawata H, Horii M, Fujimoto S, Saito Y
  • Journal Title: Internal Medicine. in press
• [Journal Article] Feasibility of evaluating epicardial fat using dual gradient-echo in-phase and opposed-phase magnetic resonance imaging. (2011)
  • Author(s): Okayama S, Somekawa S, Uemura S, Kubota Y, Saito Y
  • Journal Title: Acta Radiologica. in press
• [Journal Article] Low-dose Aspirin Therapy in Patients With Type 2 Diabetes Mellitus and Reduced Glomerular Filtration Rate : Subanalysis from the JPAD Trial. (2011)
  • Author(s): Saito Y, Morimoto T, Ogawa H, Nakayama M, Uemura S, Doi N, Jinnouchi H, Waki M, Soejima H, Sugiyama S, Okada S, Akai Y
  • Journal Title: Diabetes Care. 34 Pages: 280-285
• [Journal Article] Clinical significance of papillary muscle late enhancement detected via cardiac magnetic resonance imaging in patients with single old myocardial infarction. (2011)
  • Author(s): Okayama S, Uemura S, Soeda T, Onoue K, Somekawa S, Ishigami K, Watanabe M, Nakajima T, Fujimoto S, Saito Y
  • Journal Title: Int J Cardiol. 7;146(Epub 2010 May 14) Pages: 73-79
• [Journal Article] Vasodilator therapy with hydralazine induces angiotensin AT receptor-mediated cardiomyocyte growth in mice lacking guanylyl cyclase-A. (2010)
  • Author(s): Li Y, Saito Y, Kuwahara K, Rong X, Kishimoto I, Harada M, Horiuchi M, Murray M, Nakao K
  • Journal Title: Br J Pharmacol. 159 Pages: 1133-1142
• [Journal Article] Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity. (2010)
  • Author(s): Okada S, Kozuka C, Masuzaki H, Yasue S, Ishii-Yonemoto T, Tanaka T, Yamamoto Y, Noguchi M, Kusakabe T, Tomita T, Fujikura J, Ebihara K, Hosoda K, Sakaue H, Kobori H, Ham M, Lee YS, Kim JB, Saito Y, Nakao K
  • Journal Title: Metabolism. 59 Pages: 1241-1251
• [Journal Article] An ultrasound-responsive nano delivery system of tissue-type plasminogen activator for thrombolytic therapy. (2010)
  • Author(s): Uesugi Y, Kawata H, Jo J, Saito Y, Tabata Y
  • Journal Title: J Control Release. 15;147 Pages: 269-277
• [Journal Article] Letter by Di Marco and Brand regarding article, "Reduction of circulating soluble fms-like tyrosine kinase-1 plays a significant role in renal dysfunction-associated aggravation of atherosclerosis". (2010)
  • Author(s): Uemura S, Onoue K, Saito Y
  • Journal Title: Circulation. 122 Pages: e416-e417
• [Journal Article] Resolution of mesangial light chain deposits 3 years after high-dose melphalan with autologous peripheral blood stem cell transplantation. (2010)
  • Author(s): Harada K, Akai Y, Sakan H, Yamaguchi Y, Nakatani K, Iwano M, Saito Y
  • Journal Title: Clin Nephrol. 74 Pages: 384-388
• [Journal Article] Still Searching for a New Therapeutic Strategy for Acute Myocardial Infarction. (2010)
  • Author(s): Saito Y
  • Journal Title: Circ J. 25;74 Pages: 2290-2292
• [Journal Article] Aspirin for the primary prevention of cardiovascular events in patients with peripheral artery disease or diabetes mellitus. Analyses from the JPAD, POPADAD and AAA trials. (2010)
  • Author(s): Soejima H, Morimoto T, Saito Y, Ogawa H
  • Journal Title: Thromb Haemost. 104 Pages: 1085-1088
• [Journal Article] Roles of atrial natriuretic peptide and its therapeutic use. (2010)
  • Author(s): Saito Y
  • Journal Title: J Cardiol. 56 Pages: 262-2670
• [Journal Article] Contrast-enhanced computed tomographic and echocardiographic detection of intra-aortic free floating thrombus causing acute myocardial infarction (2010)
  • Author(s): Soeda T, Okayama S, Seno A, Kawakami R, Somekawa S, Takeda Y, Uemura S, Saito Y
  • Journal Title: J Cardiovasc Comput Tomogr. (Epub ahead of print)
• [Journal Article] Establishment of sandwich ELISA for soluble alpha-Klotho measurement : Age-dependent change of soluble alpha-Klotho levels in healthy subjects. (2010)
  • Author(s): Yamazaki Y, Imura A, Urakawa I, Shimada T, Murakami J, Aono Y, Hasegawa H, Yamashita T, Nakatani K, Saito Y, Okamoto N, Kurumatani N, Namba N, Kitaoka T, Ozono K, Sakai T, Hataya H, Ichikawa S, Imel EA, Econs MJ, Nabeshima Y.
  • Journal Title: Biochem Biophys Res Commun. 30;398 Pages: 513-518
• [Journal Article] Imaging Mass Spectrometry to Accurately Diagnose Fabry's Disease. (2010)
  • Author(s): Onoue K, Zaima N, Sugiura Y, Isojima T, Okayama S, Horii M, Akai Y, Uemura S, Takemura G, Sakuraba H, Sakaguchi Y, Setou M, Saito Y
  • Journal Title: Circ J. 24;75 Pages: 221-223
• [Journal Article] Dual Gradient-echo In-phase and Opposed-phase Magnetic Resonance Imaging to Evaluate Lipomatous Metaplasia in Patients with Old Myocardial Infarction. (2010)
  • Author(s): Okayama S, Uemura S, Sugimoto H, Enomoto S, Onoue K, Omori S, Soeda T, Somekawa S, Ishigami K, Watanabe M, Nakajima T, Kubota Y, Saito Y
  • Journal Title: Magn Reson Med Sci. 9 Pages: 85-89
• [Journal Article] Congenital isolated biventricular diverticula evaluated by cardiac computed tomography and magnetic resonance imaging. (2010)
  • Author(s): Okayama S, Uemura S, Soeda T, Seno A, Onoue K, Ishigami K, Horii M, Saito Y
  • Journal Title: Heart Lung Circ. 19 Pages: 630-632
• [Journal Article] A pediatric case of hypertrophic cardiomyopathy with mid-ventricular obstruction incidentally detected by electrocardiography. (2010)
  • Author(s): Okayama S, Fujimoto S, Tsutsumi T, Onoue K, Horii M, Uemura S, Sakaguchi Y, Saito Y
  • Journal Title: Journal of Cardiology Cases. in press
• [Journal Article] Fractalkine expression and CD16+ monocyte accumulation in glomerular lesions: association with their severity and diversity in lupus models. (2010)
  • Author(s): Nakatani K, Yoshimoto S, Iwano M, Asai O, Samejima K, Sakan H, Terada M, Hasegawa H, Nose M, Saito Y
  • Journal Title: Am J Physiol Renal Physiol. 299 Pages: F207-F216
• [Journal Article] The Homeobox Gene HEX Regulates Hepatocyte Differentiation from ES cell-Derived Endoderm. (2010)
  • Author(s): Kubo A, Kim Y. H, Irion S, Kasuda S, Takeuchi M, Ohashi K, Iwano M, Dohi Y, Saito Y, Snodgrass R, Keller G
  • Journal Title: Hepatology. 51 Pages: 633-641
• [Journal Article] A novel Thr56Met mutation of the autosomal recessive hypercholesterolemia gene associated with hypercholesterolemia. (2010)
  • Author(s): Harada K, Miyamoto Y, Morisaki H, Ohta N, Yamanaka I, Kokubo Y, Makino H, Harada-Shiba M, Okayama A, Tomoike H, Okamura T, Saito Y, Yoshimasa Y, Morisaki T
  • Journal Title: J Atheroscler Thromb. 26;17 Pages: 131-140
• [Journal Article] Role of cardiac computed tomography in planning and evaluating percutaneous transluminal septal myocardial ablation for hypertrophic obstructive cardiomyopathy. (2010)
  • Author(s): Okayama S, Uemura S, Soeda T, Horii M, Saito Y
  • Journal Title: J Cardiovasc Comput Tomogr. 4 Pages: 62-65
• [Journal Article] Novel application of black-blood echo-planar imaging to the assessment of myocardial infarction. (2010)
  • Author(s): Okayama S, Uemura S, Watanabe M, Morikawa Y, Onoue K, Soeda T, Iwama H, Somekawa S, Takeda Y, Uramoto H, Kobayashi Y, Saito Y
  • Journal Title: Heart and Vessel. 25 Pages: 104-112
• [Journal Article] Dual-single photon emission computed tomography and contrast-enhanced magnetic resonance imaging to evaluate dissimilar features of apical hypertrophic cardiomyopathy. (2010)
  • Author(s): Okayama S, Kawata H, Sung JH, Okada S, Nishida T, Onoue K, Soeda T, Uemura S, Saito Y
  • Journal Title: Cardiol J. 17 Pages: 306-311
• [Journal Article] Non-contrast MRI for the evaluation of hydronephrotic and dysfunctioning kidney secondary to testicular cancer. (2009)
  • Author(s): Okayama S, Matsui M, Somekawa S, Iwano M, Saito Y.
  • Journal Title: Ren Fail. 31 Pages: 153-158
• [Journal Article] Coronary spasm preferentially occurs at branch points : An angiographic comparison with atherosclerotic plaque. (2009)
  • Author(s): Nakagawa H, Morikawa Y, Mizuno Y, Harada E, Ito T, Matsui K, Saito Y, Yasue H.
  • Journal Title: Circ Cardiovasc Intervent. 2 Pages: 97-104
• [Journal Article] Treatment with recombinant placental growth factor (PlGF) enhances both angiogensis and arteriogenesis and improves survival after myocardial infarction. (2009)
  • Author(s): Takeda Y, Uemura S, Iwama H, Imagawa K, Nishida T, Onoue K, Takemoto Y, Soeda T, Okayama S, Somekawa S, Ishigami K, Takaoka M, Kawata H, Kubo A, Horii M, Nakajima T, Saito Y.
  • Journal Title: Circ J. 73 Pages: 1674-1682
• [Journal Article] Regulation of aldosterone and cortisol production by the transcriptional repressor neuron restrictive silencer factor. (2009)
  • Author(s): Somekawa S, Imagawa K, Naya N, Takemoto Y, Onoue K, Okayama S, Takeda Y, Kawata H, Horii M, Nakajima T, Uemura S, Mochizuki N, Saito Y.
  • Journal Title: Endocrinology. 50 Pages: 3110-3117
• [Journal Article] Human placental ectonucleoside triphosphate diphosphohydrolase gene transfer via gelatin-coated stents prevents in-stent thrombosis. (2009)
  • Author(s): Takemoto Y, Kawata H, Soeda T, Imagawa K, Somekawa S, Takeda Y, Uemura S, Matsumoto M, Fujimura Y, Jo J, Kimura Y, Tabata Y, Saito Y.
  • Journal Title: Arterioscler Thromb Vasc Biol. 29 Pages: 857-862
• [Journal Article] Guanylyl cyclase-A inhibits angiotensin II type 2 receptor-mediated pro-hypertrophic signaling in the heart. (2009)
  • Author(s): Li Y, Saito Y, Kuwahara K, Rong X, Kishimoto I, Harada M, Adachi Y, Nakanishi M, Kinoshita H, Horiuchi M, Murray M, Nakao K.
  • Journal Title: Endocrinology. 150 Pages: 3759-3765
• [Journal Article] Epithelial-mesenchymal transition as an explanation for podocyte depletion in diabetic nephropathy. (2009)
  • Author(s): Yamaguchi Y, Iwano M, Suzuki D, Nakatani K, Kimura K, Harada K, Kubo A, Akai Y, Toyoda M, Kanauchi M, Eric G Neilson, Saito Y.
  • Journal Title: Am J Kidney Dis. 54 Pages: 653-664
• [Journal Article] Morphological features of coronary arteries in patients with coronary spastic angina : Assessment with intracoronary optical coherence tomography. (2009)
  • Author(s): Morikawa Y, Uemura S, Ishigami K, Soeda T, Okayama S, Takemoto Y, Onoue K, Somekawa S, Nishida T, Takeda Y, Kawata H, Horii M, Saito Y.
  • Journal Title: Int J Cardiol. (Epub ahead of print)
• [Journal Article] Long term follow-up of neointimal coverage of sirolimus-eluting stents: Evaluation with optical coherencetomography. (2009)
  • Author(s): Ishigami K, Uemura S, Morikawa Y, Soeda T, Okayama S, Nishida T, Takemoto Y, Onoue K, Somekawa S, Takeda Y, Kawata H, Horii M, Saito Y.
  • Journal Title: Circ J. 3 Pages: 2300-2307
• [Journal Article] Usefulness of soluble Fms-like tyrosine kinase 1 as a biomarker of acute severe heart failure in patients with acute myocardial infarction. (2009)
  • Author(s): Onoue K, Uemura S, Takeda Y, Somekawa S, Iwama H, Nishida T, Morikawa Y, Nakagawa H, Tsutsumi T, Sung J. H, Takemoto Y, Soeda T, Okayama S, Ishigami K, Kawata H, Horii M, Nakajima T, Saito Y.
  • Journal Title: Am J Cardiol. 104 Pages: 1478-1483
• [Journal Article] Periadventitial adipose tissue plays a critical role in vascular remodeling. (2009)
  • Author(s): Takaoka M, Nagata D, Kihara S, Shimomura I, Kimura Y,Tabata Y, Saito Y, Nagai R, Sata M.
  • Journal Title: Circ Res. 105 Pages: 906-911
• [Journal Article] Reduction of circulating soluble fms-like tyrosine kinase-1 plays a significant role in renal dysfunction-associated aggravation of atherosclerosis. (2009)
  • Author(s): Onoue K, Uemura S, Takeda Y, Somekawa S, Iwama H, Imagawa K, Nishida T, Morikawa Y, Takemoto Y, Asai O, Soeda T, Okayama S, Ishigami K, Nakatani K, Kawata H, Horii M, Nakajima T, Akai Y, Iwano M, Saito Y.
  • Journal Title: Circulation. 15;120 Pages: 2470-2477
• [Journal Article] Prediction of corticosteroid responsiveness based on fibroblast-specific protein 1 (FSP1) in patients with IgA nephropathy. (2008)
  • Author(s): Harada K, Akai Y, Yamaguchi Y, Kimura K, Nishitani Y, Nakatani K, Iwano M, Saito Y.
  • Journal Title: Nephrol Dial Transplant. 23 Pages: 3152-3159
• [Journal Article] A case of autoimmune hepatitis exacerbated by the administration of etanercept in the patient with rheumatoid arthritis. (2008)
  • Author(s): Harada K, Akai Y, Koyama S, Ikenaka Y, Saito Y.
  • Journal Title: Clin Rhrumatol. 27 Pages: 1063-1066
• [Journal Article] Continuing improvement of cardiac sympathetic activity on 123I-MIBG scintigraphy in a patient with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation. (2008)
  • Author(s): Okayama S, Uemura S, Kawata H, Horii M, Saito Y.
  • Journal Title: J Nucl Cardiol. 15 Pages: e31-e34
• [Journal Article] The Specific Mineralocorticoid Receptor Blocker Eplerenone Attenuates Left Ventricular Remodeling in Mice Lacking the Gene Encoding Guanylyl Cyclase-A. (2008)
  • Author(s): Q Zhang, Saito Y, Naya N, Imagawa K, Somekawa S, Kawata H, Takeda Y, Uemura S, Kishimoto I, Nakao K.
  • Journal Title: Hypertens Res. 31 Pages: 1251-1256
• [Journal Article] Effects of a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers. (2008)
  • Author(s): Yasue H, Mizuno Y, Harada E, Itoh T, Nakagawa H, Nakayama M, Ogawa H, Tayama S, Honda T, Hokimoto S, Ohshima S, Hokamura Y, Kugiyaama K, Horie M, Yoshimura M, Harada M, Uemura S, Y. Saito.
  • Journal Title: J Am Coll Cardiol. 51 Pages: 1742-1748
• [Journal Article] Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. (2008)
  • Author(s): Matoba S, Tatsumi T, Murohara T, Imaizumi T, Katsuda Y, Ito M, Saito Y, Uemura S, H Suzuki, Fukumoto S, Yamamoto Y, Onodra R, Fukushima S, Matsubara H.
  • Journal Title: Am Heart J. 156 Pages: 1010-1018
• [Journal Article] Establishment of embryonic stem cells secreting human factor VIII for cell-based treatment of hemophilia A. (2008)
  • Author(s): Kasuda S, Kubo A, Sakurai Y, Irion S, Ohashi K, Tatsumi K, Nakajima Y, Saito Y, Hakake K, Pipe SW, Shima M, Yoshioka A.
  • Journal Title: J Thromb Haemost. 6 Pages: 1352-1359
• [Journal Article] Progression of non-culprit coronary artery atherosclerosis after acute myocardial infarction in comparison with stable angina pectoris. (2008)
  • Author(s): Okayama S, Uemura S, Nishida T, Morikawa Y, Onoue K, Takemoto Y, Soeda T, Somekawa S, Ishigami K, Takeda Y, Horii M, Kawata H, Takaoka M, Nakajima T, Saito Y.
  • Journal Title: J Atheroscler Thromb 15 Pages: 228-234
• [Journal Article] Acute myocardial infarction as a systemic prothrombotic condition evidenced by increased von willebrand factor protein over ADAMTS13 activity in coronary and systemic circulation. (2008)
  • Author(s): Horii M, Uemura S, Uemura M, Matsumoto M,Ishizashi H, Imagawa K, Iwama H, Takeda Y, Kawata H, Nakajima T, Fujimura Y, Saito Y.
  • Journal Title: Heart and Vessel. 23 Pages: 301-307
• [Journal Article] On behalf of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Trial Investigators*. (2008)
  • Author(s): Ogawa H, Nakayama M, Morimoto T, Uemura S, Kanauchi,M, Doi N, Jinnouchi H, Sugiyama S, Saito Y.
  • Journal Title: JAMA 300 Pages: 2134-2141
• [Presentation] Optical Coherence Tomography-Based Complex Plaque Characteristics Predict the Subsequent Progression of Non-culprit Lesion in Patients with Percutaneous Coronary Intervention. (2010)
  • Author(s): Uemura S, Ishigami K, Soeda T, Sung J, Nakagawa H, Tsutsumi T, Okayama S, Kawata H, Horii M, Saito Y
  • Organizer: American Heart Association Scientific Session
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101113-20101117
• [Presentation] Development of the New Drug Delivery System with Ultrasound for Coronary Thrombosis. (2010)
  • Author(s): Kawata H, Soeda T, Takemoto Y, Sung J, Uemura S, Uesugi Y, Jo J, Tabata Y, Umaki K, Kato K, Saito Y
  • Organizer: American Heart Association Scientific Session 2010
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101113-20101117
• [Presentation] Better Neointimal Formation of Paclitaxel Eluting Stent of the Patient with Multiple Risk Factor -Optical coherence tomography study-. (2010)
  • Author(s): Ishigami K, Uemura S, Sung J, Soeda T, Okayama S, Kawata H, Horii M, Saito Y
  • Organizer: American Heart Association Scientific Session 2010
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101113-20101117
• [Presentation] Efficacy of Low-dose Aspirin Therapy for Primary Prevention of Atherosclerotic Events Depends on the Severity of Diabetes : a subanalysis of JPAD trial. (2010)
  • Author(s): Okada S, Morimoto T, Ogawa H, Nakayama H, Sakuma M, Uemura S, Kanauchi M, Doi N, Jinnouchi H, Soejima H, Sugihara S, Waki M, Kawano T, Saito Y
  • Organizer: American Heart Association Scientific Session 2010 November
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101113-20101117
• [Presentation] Diffuse Intimal Thickness without Lipid or Calcium Content at Branch Points is a Characteristic Feature of Coronary Artery in Patitents with Coronary Spastic Angina : Optical Coherence Tomography Analysis. (2010)
  • Author(s): Nakagawa H, Uemura S, Horii M, Ishigami K, Soeda T, Sung J, Somekawa S, Okayama S, Morikawa Y, Mizuno Y, Harada E, Yasue H, Saito Y
  • Organizer: American Heart Association Scientific Session 2010
  • Place of Presentation: Chicago, USA
  • Year and Date: 20101113-20101117
• [Remarks] ホームページ等
  • URL: http://www.naramed-u.ac.jp/~1int/
• [Patent(Industrial Property Rights)] 血栓溶解酵素含有複合体 (2010)
  • Inventor(s): 斎藤能彦・川田 啓之・田畑泰彦
  • Industrial Property Rights Holder: 公立大学法人奈良県立医科大学・国立大学法人京都大学
  • Industrial Property Number: 特願,2010-120535
  • Filing Date: 2010-05-26