The mechanism of vascular calcification and endothelial dysfunction in chronic kidney disease

• Project/Area Number: 25461140
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kurume University
• Principal Investigator: KAJIMOTO HIDEMI 久留米大学, 医学部, 助教 (50349700)
• Co-Investigator(Kenkyū-buntansha): 岩元 美子 久留米大学, 医学部, 助教 (30597422) ; 打和 大幹 久留米大学, 医学部, 助教 (30624506) ; 甲斐 久史 久留米大学, その他部局等, 教授 (60281531)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 慢性腎不全 / 血管病 / 血管内皮機能 / 血管石灰化

Outline of Final Research Achievements

BMP receptor signaling has a pivotal role in endothelial dysfunction, in addition to osteogenic differentiation of VSMCs, in the early stage of CKD without vascular remodeling. An increase in PTEN protein is involved in the mechanism by which BMP receptor activation inhibits Akt-eNOS signaling in CKD. Our observations suggest that BMP receptor signaling would be a promising target for the prevention and treatment of both endothelial dysfunction and vascular calcification in the early stage of CKD patients.

Research Products

• [Journal Article] Interleukin-1β is associated with coronary endothelial dysfunction in patients with mTOR inhibitor-eluting stent implantation. (2017)
  • Author(s): Chibana H, Kajimoto H, Ueno T, Yokoyama S, Sasaki K, Ohtsuka M, Koiwaya H, Nakayoshi T, Mitsutake Y, Itaya N, Sasaki M, Fukumoto Y.
  • Journal Title: Heart and Vessels Volume: 1 Issue: 7 Pages: 823-832
  • DOI: 10.1007/s00380-017-0947-x
  • Peer Reviewed / Open Access
• [Journal Article] BMP type I receptor inhibition attenuates endothelial dysfunction in mice with chronic kidney disease (2014)
  • Author(s): Kajimoto, H. Kai, H. Aoki, H. Uchiwa, H. Aoki, Y. Yasuoka, S. Anegawa, T. Mishina, Y. Suzuki, A. Fukumoto, Y. Imaizumi, T.
  • Journal Title: Kidney international Volume: 87 Issue: 1 Pages: 128-36
  • DOI: 10.1038/ki.2014.223
  • Peer Reviewed
• [Journal Article] FOXO4-Knockdown Suppresses Oxidative Stress-Induced Apoptosis of Early Pro-Angiogenic Cells and Augments Their Neovascularization Capacities in Ischemic Limbs (2014)
  • Author(s): Takaharu Nakasyohi
  • Journal Title: PLOS one Volume: 9 Issue: 3 Pages: e92626-e92626
  • DOI: 10.1371/journal.pone.0092626
  • Peer Reviewed / Open Access
• [Journal Article] Large Blood Pressure Variability Aggravates Arteriolosclerosis and Cortical Sclerotic Changes in the Kidney in Hypertensive Rats (2014)
  • Author(s): Aoki Y, Kai H, Kajimoto H, Kudo H, Takayama N, Yasuoka S, Anegawa T, Iwamoto Y, Uchiwa H, Fukuda K, Kage M, Kato S, Fukumoto Y, Imaizumi T.
  • Journal Title: Circulation Journal Volume: 78 Issue: 9 Pages: 2284-2291
  • DOI: 10.1253/circj.CJ-14-0027
  • NAID: 130004677614
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Journal Article] Triiodothyronine Activates Lactate Oxidation Without Impairing Fatty Acid Oxidation and Improves Weaning From Extracorporeal Membrane Oxygenation (2014)
  • Author(s): Kajimoto M, Ledee D, Xu C, Kajimoto H, Isern N, Portman M.
  • Journal Title: Circulation Journal Volume: 78 Issue: 12 Pages: 2867-2875
  • DOI: 10.1253/circj.CJ-14-0821
  • NAID: 130004701549
  • ISSN: 1346-9843, 1347-4820
  • Peer Reviewed / Open Access
• [Presentation] 腎ー血管連関とeNOS signaling：古くて新しい分子メカニズム (2013)
  • Author(s): 梶本英美
  • Organizer: 第49回日本小児循環器学会総会・学術集会
  • Place of Presentation: 東京
• [Presentation] Bone Morphogenetic Protein Receptor Activation Plays a Crucial Role in Endothelial Dysfunction and Osteogenic Differentiation in Mice with Chronic Kidney Disease. (2013)
  • Author(s): Hidemi Kajimoto
  • Organizer: ESC Congress 2013
  • Place of Presentation: Amsterdam, The Netherlands
• [Presentation] BMP type I Receptor Inhibition Reduces Endothelial Dysfunction and Vascular Osteogenic Differentiation in Mice with Chronic Kidney Disease. (2013)
  • Author(s): Hidemi Kajimoto
  • Organizer: American Heart Association’s Scientific Sessions 2013
  • Place of Presentation: Dallas, USA