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A Nobel Protein TMEM100 and Pulmonary Hypertension and Right-sided Heart Failure.

Research Project

Project/Area Number 25293187
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionNara Medical University

Principal Investigator

SAITO YOSHIHIKO  奈良県立医科大学, 医学部, 教授 (30250260)

Co-Investigator(Kenkyū-buntansha) ONOUE Kenji  奈良県立医科大学, 医学部第1内科, 助教 (90510173)
染川 智  奈良県立医科大学, 医学部, 助教 (90453167)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2013: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
KeywordsTMEM100 / 肺高血圧 / 右心不全 / BMP9/10 / IP3受容体 / GPR78 / ALK1 / 血管新生 / BMP9
Outline of Final Research Achievements

The mechanism for pulmonary arterial hypertension (PAH) and its complication, right-sided heart failure is unknown. Using cDNA array analyses in the right ventricular tissues in the rats with monocrotaline-induced pulmonary hypertension, we have focused TMEM100, which is 20kD protein located in endo-cyto plasmic reticulum. Interestingly, TMEM100 expression is upregulated in cultured human umbilical arterial endothelial cells by BMP9/10, specific ligands for ALK1/BMPR2 receptors, recognized as causative genes for PAH by the linkage analysis in familial PAH. Thus, it is expected that TMEM100 is involved in the pathogenesis of PAH and its complication, right-sided heart failure.
Because of mice lacking the tmem100 gene is embryonic lethal, we generated inducible knockout mice of the tmem100 gene. Unfortunately, in spite of several experimental pulmonary arterial hypertension models, we have not found the evidence that TMEM100 is involved in the pathogenesis of PAH.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (34 results)

All 2015 2014 2013 Other

All Journal Article (27 results) (of which Peer Reviewed: 27 results,  Open Access: 17 results,  Acknowledgement Compliant: 8 results) Presentation (5 results) Remarks (2 results)

  • [Journal Article] Impairment of endothelial-mesenchymal transformation during atrioventriucular cushion formation in Tmem100 null embryo2015

    • Author(s)
      Mizuta K., Sakabe M., Ioka T., Hashimoto A., Ioka T., Sakai C., Okumura K., Hattammaru M., Fujita M., Araki M., Somekawa S., Saito Y., Nakagawa O
    • Journal Title

      Developmental Dynamics

      Volume: 244 Issue: 1 Pages: 31-42

    • DOI

      10.1002/dvdy.24216

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Proteinuria and Reduced Estimated Glomerular Filtration Rate Are Independent Risk Factors for Contrast-Induced Nephropathy After Cardiac Catheterization.2015

    • Author(s)
      Saito Y, Watanabe M, Aonuma K, Hirayama A, Tamaki N, Tsutsui H, Murohara T, Ogawa H, Akasaka T, Yoshimura M, Sato A, Takayama T, Sakakibara M, Suzuki S, Ishigami K, Onoue K; CINC-J study investigators.
    • Journal Title

      Circ J.

      Volume: 79 Pages: 1624-30

    • NAID

      130005083936

    • Related Report
      2015 Annual Research Report 2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Major Non-Cardiac Surgery Is a Risk Factor for Rapid Hemodynamic Progression of Non-Rheumatic Aortic Stenosis2015

    • Author(s)
      Mizuno R, Yamagami S, Higashi T, Nakada Y, Takeda Y, Okayama S, Fujimoto S, Saito Y.
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 4 Pages: 867-872

    • DOI

      10.1253/circj.CJ-14-1111

    • NAID

      130005130262

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of coronary artery disease and cardiac morphology and function in patients with hypertrophic cardiomyopathy, using cardiac computed tomography.2015

    • Author(s)
      Okayama S, Soeda T, Kawakami R, Takami Y, Somekawa S, Ueda T, Sugawara Y, Matsumoto T, Sung JH, Nishida T, Uemura S, Saito Y.
    • Journal Title

      Heart Vessels.

      Volume: 30 Issue: 1 Pages: 28-35

    • DOI

      10.1007/s00380-013-0452-9

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasma Renin Activity Is a Strong and Independent Prognostic Indicator in Patients With Acute Decompensated Heart Failure Treated With Renin-Angiotensin System Inhibitors2015

    • Author(s)
      Ueda T, Kawakami R, Nishida T, Onoue K, Soeda T, Okayama S, Takeda Y, Watanabe M, Kawata H, Uemura S, Saito Y.
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 6 Pages: 1307-1314

    • DOI

      10.1253/circj.CJ-14-1203

    • NAID

      130005073144

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Placental Growth Factor As A Predictor Of Cardiovascular Events In Patients With Chronic Kidney Disease from the Novel Assessment of Risk management for Atherosclerotic diseases in Chronic Kidney Disease (NARA-CKD) Study.2015

    • Author(s)
      Matsui M, Uemura S, Takeda Y, Samejima K, Matsumoto T, Hasegawa A Tsushima H, Hoshino E, Ueda T, Morimoto K, Okamoto K, Okada S, Onoue K, Okayama S, Kawata H, Kawakami R, Maruyama N, Akai Y, Iwano M, Shiiki H, Saito Y, for the NARA-CKD investigators.
    • Journal Title

      J Am Soc Nephrol.

      Volume: Mar 18 Issue: 11 Pages: 2871-2881

    • DOI

      10.1681/asn.2014080772

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Clinical Presentation, Management and Outcome of Japanese Patients With Acute Myocardial Infarction in the Troponin Era – Japanese Registry of Acute Myocardial Infarction Diagnosed by Universal Definition (J-MINUET) –2015

    • Author(s)
      Ishihara M, Fujino M, Ogawa H, Yasuda S, Noguchi T, Nakao K, Ozaki Y, Kimura K, Suwa S, Fujimoto K, Nakama Y, Morita T, Shimizu W, Saito Y, Tsujita K, Nishimura K, Miyamoto Y; J-MINUET investigators.
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 6 Pages: 1255-1262

    • DOI

      10.1253/circj.CJ-15-0217

    • NAID

      130005073152

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evaluation of cardiac prognosis in hemodialysis patients by using coronary computed tomography angiography and thallium single photon emission computed tomography: a retrospective study2015

    • Author(s)
      Okayama S, Tanaka K, Kawata H, Dote Y, Matsui M, Samejima K, Takeda Y, Uemura S, Saito Y
    • Journal Title

      Experimental & Clinical Cardiology.

      Volume: in press

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac amyloidosis incidentally detected using technetium-99m hydroxymethylene diphosphonate bone scintigraphy in a patient with prostate cancer.2015

    • Author(s)
      Okayama S, Sugimoto M, Nakano T, Onoue K, Sakaguchi Y, Uemura S, Saito Y.
    • Journal Title

      IJC Heart & Vessels.

      Volume: 4 Pages: 213-214

    • DOI

      10.1016/j.ijchv.2014.04.010

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Author's reply.[Cardiomyopathy: progress in diagnosis and treatments. Topics: III. Diagnosis leading to selection of therapy: 2. Biomarker]2014

    • Author(s)
      Horii M, Saito Y.
    • Journal Title

      J Cardiol.

      Volume: 64 Issue: 3 Pages: 242-242

    • DOI

      10.1016/j.jjcc.2014.01.008

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppressed soluble Fms-like tyrosine kinase-1 production aggravates atherosclerosis in chronic kidney disease2014

    • Author(s)
      Matsui M, Takeda Y, Uemura S, Matsumoto T, Seno A, Onoue K, Tsushima H, Morimoto K, Soeda T, Okayama S, Somekawa S, Samejima K, Kawata H, Kawakami R, Nakatani K, Iwano M, Saito Y.
    • Journal Title

      Kidney Int

      Volume: 85(2) Issue: 2 Pages: 393-403

    • DOI

      10.1038/ki.2013.339

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Therapeutic Benefits of Tocilizumab Vary in Different Organs of a Patient with AA Amyloidosis.2014

    • Author(s)
      Matsui M, Okayama S, Tsushima H, Samejima K, Kanki T, Hasegawa A, Morimoto K, Akai Y, Takano M, Uemura S, Ohbayashi C, Saito Y.
    • Journal Title

      Case Rep Nephrol.

      Volume: 823093 Pages: 1-6

    • DOI

      10.1155/2014/823093

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Atrial Natriuretic Peptide Locally Counteracts the Deleterious Effects of Cardiomyocyte Mineralocorticoid Receptor Activation.2014

    • Author(s)
      Nakagawa H, Oberwinkler H, Nikolaev VO, Gabner B, Umbenauer S, Wagner H, Saito Y, Baba HA, Frantz S, Kuhn M.
    • Journal Title

      Circ Heart Fail.

      Volume: 7 Issue: 5 Pages: 814-821

    • DOI

      10.1161/circheartfailure.113.000885

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Refractory High Output Heart Failure in a Patient with Primary Mitochondrial Respiratory Chain Disease2014

    • Author(s)
      Nakagawa H, Okayama S, Kamon D, Nakano T, Onoue K, Kawakami R, Horii M, Sakaguchi Y, Uemura S, Takemura G, Saito Y.
    • Journal Title

      Internal Medicine

      Volume: 53 Issue: 4 Pages: 315-319

    • DOI

      10.2169/internalmedicine.53.1386

    • NAID

      130003392649

    • ISSN
      0918-2918, 1349-7235
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three different morphologies of inferior vena cava thrombosis: case reports.2014

    • Author(s)
      Okayama S, Nakada Y, Uemura S, Saito Y.
    • Journal Title

      Case Rep Vasc Med.

      Volume: 349213 Pages: 1-3

    • DOI

      10.1155/2014/349213

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Three different morphologies of inferior vena cava thrombosis2014

    • Author(s)
      Okayama.S, Nakada Y, Uemura S, Saito Y.
    • Journal Title

      Case Rep in Vasc Med.

      Volume: Mar 4

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cardiomyopathy: progress in diagnosis and treatments. Topics: III. Diagnosis leading to selection of therapy: 2. Biomarker.2014

    • Author(s)
      Onoue K, Nkano T, Saito Y.
    • Journal Title

      Nihon Naika Gakkai Zasshi 103: 345-52, 2014

      Volume: 103 Pages: 345-352

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduced renal α-Klotho expression in CKD patients and its effect on renal phosphate handling and vitamin D metabolism.2014

    • Author(s)
      Sakan H, Nakatani K, Asai O, Imura A, Tanaka T, Yoshimoto S, Iwamoto N, Kurumatani N, Iwano M, Nabeshima Y, Konishi N, Saito Y.
    • Journal Title

      PLoS One.

      Volume: 9(1):e86301 Issue: 1 Pages: 1-1

    • DOI

      10.1371/journal.pone.0086301

    • Related Report
      2014 Annual Research Report 2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Japanese Society of Hypertension guidelines for the management of hypertension (JSH 2014)2014

    • Author(s)
      Shimamoto K, Hasebe N et al
    • Journal Title

      Hypertens Res

      Volume: 37 Issue: 4 Pages: 253

    • DOI

      10.1038/hr.2014.20

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Worsening of renal function during 1 year after hospital discharge is a strong and independent predictor of all-cause mortality in acute decompensated heart failure.2014

    • Author(s)
      Ueda T, Kawakami R, Sugawara Y, Okada S, Nishida T, Onoue K, Soeda T, Okayama S, Takeda Y, Watanabe M, Kawata H, Uemura S, Saito Y.
    • Journal Title

      J Am Heart Assoc.

      Volume: 3 Issue: 6 Pages: 001174-001174

    • DOI

      10.1161/jaha.114.001174

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Colocalization of thin-cap fibroatheroma and spotty calcification is a powerful predictor of procedure-related myocardial injury after elective coronary stent implantation.2014

    • Author(s)
      Ueda T, Uemura S, Watanabe M, Sugawara Y, Soeda T, Okayama S, Takeda Y, Kawata H, Kawakami R, Saito Y.
    • Journal Title

      Coron Artery Dis. 25:384-91, 2014.

      Volume: 25 Issue: 5 Pages: 384-391

    • DOI

      10.1097/mca.0000000000000114

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Noncardiovascular death, especially infection, is a significant cause of death in elderly patients with acutely decompensated heart failure.2014

    • Author(s)
      Ueda T, Kawakami R, Horii M, Sugawara Y, Matsumoto T, Okada S, Nishida T, Soeda T, Okayama S, Somekawa S, Takeda Y, Watanabe M, Kawata H, Uemura S, Saito Y.
    • Journal Title

      J Card Fail.20:174-80, 2014

      Volume: 20 Issue: 3 Pages: 174-180

    • DOI

      10.1016/j.cardfail.2013.12.007

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Side branch complication after a single-stent crossover technique: prediction with frequency domain optical coherence tomography.2014

    • Author(s)
      Watanabe M, Uemura S, Sugawara Y, Ueda T, Soeda T, Takeda Y, Kawata H, Kawakami R, Saito Y.
    • Journal Title

      Coron Artery Dis. 25: 321-9, 2014

      Volume: 25 Issue: 4 Pages: 321-329

    • DOI

      10.1097/mca.0000000000000091

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppressed Soluble Fms-Like Tyrosine Kinase-1 Production Aggravates Atherosclerosis in CKD : Evaluation by Circulating sFlt-1 Levels after Low-Dose Heparin Injection.2014

    • Author(s)
      Matsui M, Takeda Y, Uemura S, Matsumoto T, Seno A, Onoue K, Tsushima H, Morimoto K, Soeda T, Okayama S, Somekawa S, Samejima K, Kawata H, Kawakami R, Nakatani K, Iwano M, Saito Y.
    • Journal Title

      Kid Int.

      Volume: 85 Pages: 393-403

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nuclear accumulation of androgen receptor in gender difference of dilated cardiomyopathy due to lamin A/C mutations.2013

    • Author(s)
      Arimura T, Onoue K, Takahashi-Tanaka Y, Ishikawa T, Kuwahara M, Setou M, Shigenobu S, Yamaguchi K, Bertrand AT, Machida N, Takayama K, Fukusato M, Tanaka R, Somekawa S, Nakano T, Yamane Y, Kuba K, Imai Y, Saito Y, Bonne G, Kimura A.
    • Journal Title

      Cardiovasc Res.

      Volume: 99 Pages: 382-94

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] High mean corpuscular volume (MCV) is a new predictor of prognosis in patients with acute decompensated heart failure.2013

    • Author(s)
      Ueda T, Kawakami R, Horii M, Sugawara Y, Matsumoto T, Okada S, Nishida T, Soeda T, Okayama S, Somekawa S, Takeda Y, Watanabe M, Kawata H, Uemura S, Saito Y.
    • Journal Title

      Circ J.

      Volume: 77 Pages: 2766-71

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypertrophic cardiomyopathy and mesenteric venous thrombosis in a patient with Klinefelter syndrome.2013

    • Author(s)
      Okayama S, Uemura S, Saito Y.
    • Journal Title

      Int J Cardiol.

      Volume: 166

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Trial Investigators Long-term Use of Low-dose Aspirin Develops Proteinuria in Patients With Diabetes: A Reanalysis of JPAD Study.2013

    • Author(s)
      Okada S, Morimoto T, Ogawa H, Sakuma M, Soejima H, Ohtorii M, Nakayama M, Doi N, Akai Y, Jinnouchi H, Waki M, Sugiyama S, Uemura S, Saito Y.
    • Organizer
      American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Uremic Toxin Aggravates Atherosclerosis by Suppression of Endothelial Soluble Flt-1 Production in CKD.2013

    • Author(s)
      akeda Y, Uemura S, Matsui M, Matsumoto T, Seno A, Okada S, Nishida T, Soeda T, Okayama S, Somekawa S, Watanabe M, Kawata H, Kawakami R, Saito Y.
    • Organizer
      American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Worsening of Renal Function after One Year, Not During Hospitalization, is Stronger Predictor of Prognosis in Patients With ADHF.2013

    • Author(s)
      Ueda T, Kawakami R, Sugawara Y, Matsumoto T, Okada S, Soeda T, Okayama S, Somekawa, Takeda Y, Watanabe M, Kawata H, Uemura S, Saito Y.
    • Organizer
      American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Proximal Stent Edge Location on Thin Cap Fibroatheroma is a Predictor of In-Stent Restenosis -Optical Coherence Tomography Study.2013

    • Author(s)
      Ueda T, Uemura S, Kurokawa M, Sugawara Y, Soeda T, Takeda Y, Watanabe M, Kawata H, Kawakami R, Saito Y.
    • Organizer
      American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Annual Research Report
  • [Presentation] Side Branch Complication after Single Stent Crossover Technique: Prediction with Pre-procedural Optical Coherence Tomography Evaluation.2013

    • Author(s)
      Watanabe M, Uemura S, Sugawara Y, Ueda T, Soeda T, Takeda Y, Kawata H, Kawakami R, Saito Y.
    • Organizer
      American Heart Association
    • Place of Presentation
      Dallas, Texas, USA
    • Related Report
      2013 Annual Research Report
  • [Remarks] 奈良県立医科大学第1内科ホームページ

    • URL

      http://www.naramed-u.ac.jp/~1int/

    • Related Report
      2014 Annual Research Report
  • [Remarks] 奈良県立医科大学第1内科学教室ホームページ

    • URL

      http://www.naramed-u.ac.jp/~1int/

    • Related Report
      2013 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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