Novel Mechanisms of Chronic Heart Failure with Anemia

2011 Fiscal Year Final Research Report

• Project/Area Number: 22790737
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Hyogo Medical University
• Principal Investigator: NAITO Yoshiro 兵庫医科大学, 医学部, 講師 (10446049)
• Project Period (FY): 2010 – 2011
• Keywords: 循環器・高血圧 / 内科 / 基礎

Research Abstract

We revealed that angiotensin II type 1a receptor(AT1aR) and erythropoietin receptor(EpoR) signal pathways are involved in the mechanism of iron deficiency induced cardiac remodeling. Dietary iron-restricted EpoR rescued mice, which express EpoR only in the hematopoietic lineage, demonstrated anemia and systolic dysfunction, thereby inducing heart failure and decreasing a survival rate. On the other hand, AT1aR knock-out mice attenuated Epo secretion in response to iron deficiency. As a result, our data suggests that modulation of AT1aR and cardiac EpoR signaling may represent a therapeutic target for anemia-induced heart failure.

Research Products

• [Journal Article] Impaired expression of duodenal iron transporters in Dahl salt-sensitive heart failure rats (2011)
  • Author(s): Naito Y, Tsujino T, Fujimori Y, Sawada H, Akahori H, Hirotani S, Ohyanagi M, Masuyama T.
  • Journal Title: J Hypertens. Volume: 29 Pages: 741-748
  • Peer Reviewed
• [Journal Article] Dietary iron restriction prevents hypertensive cardiovascular remodeling in dahl salt-sensitive rats (2011)
  • Author(s): Naito Y, Hirotani S, Sawada H, Akahori H, Tsujino T, Masuyama T.
  • Journal Title: Hypertension. Volume: 57 Pages: 497-504
  • Peer Reviewed
• [Journal Article] Involvement of bone morphogenetic protein-binding endothelial regulator in aortic valve stenosis (2011)
  • Author(s): Sawada H, Naito Y, Hirotani S, Akahori H, Iwasaku T, Eguchi A, Okuhara Y, Fujii A, Ohyanagi M, Mitsuno M, Miyamoto Y, Tsujino T, Masuyama T.
  • Journal Title: Int J Cardiol. Volume: 152 Pages: 107-109
  • Peer Reviewed
• [Journal Article] Role of plasma aldosterone concentration in regression of left-ventricular mass following antihypertensive medication (2011)
  • Author(s): Yoshida C, Goda A, Naito Y, Nakaboh A, Matsumoto M, Otsuka M, Ohyanagi M, Hirotani S, Lee-Kawabata M, Tsujino T, Masuyama T.
  • Journal Title: J Hypertens. Volume: 29 Pages: 357-363
  • Peer Reviewed
• [Journal Article] Administration of angiotensin-converting enzyme inhibitors is associated with slow progression of mild aortic stenosis in Japanese patients (2011)
  • Author(s): Wakabayashi K, Tsujino T, Naito Y, Ezumi A, Lee-Kawabata M, Nakao S, Goda A, Sakata Y, Yamamoto K, Daimon T, Masuyama T.
  • Journal Title: Heart Vessels. Volume: 26 Pages: 252-257
  • Peer Reviewed
• [Journal Article] Intraleaflet hemorrhage is associated with rapid progression of degenerative aortic valve stenosis (2011)
  • Author(s): Akahori H, Tsujino T, Naito Y, Matsumoto M, Lee-Kawabata M, Ohyanagi M, Mitsuno M, Miyamoto Y, Daimon T, Hao H, Hirota S, Masuyama T.
  • Journal Title: Eur Heart J. Volume: 32 Pages: 888-896
  • Peer Reviewed
• [Journal Article] Increase in tissue and circulating pentraxin3 levels in patients with aortic valve stenosis (2010)
  • Author(s): Naito Y, Tsujino T, Akahori H, Ohyanagi M, Mitsuno M, Miyamoto Y, Hao H, Hirota S, Masuyama T.
  • Journal Title: Am Heart J. Volume: 160 Pages: 685-691
  • Peer Reviewed
• [Journal Article] Increased Serum Neopterin in Patients with Nonrheumatic Aortic Valve Stenosis (2010)
  • Author(s): Naito Y, Tsujino T, Akahori H, Matsumoto M, Ohyanagi M, Mitsuno M, Miyamoto Y, Masuyama T.
  • Journal Title: Int J Cardiol. Volume: 145 Pages: 360-361
  • Peer Reviewed
• [Journal Article] Augmented cannabinoid receptors expression in human aortic valve stenosis (2010)
  • Author(s): Naito Y, Tsujino T, Akahori H, Ohyanagi M, Mitsuno M, Miyamoto Y, Masuyama T.
  • Journal Title: Int J Cardiol. Volume: 145 Pages: 535-537
  • Peer Reviewed
• [Journal Article] Increased interleukin-18 expression in nonrheumatic aortic valve stenosis (2010)
  • Author(s): Naito Y, Tsujino T, Wakabayashi K, Matsumoto M, Ohyanagi M, Mitsuno M, Miyamoto Y, Hao H, Hirota S, Okamura H, Masuyama T.
  • Journal Title: Int J Cardiol. Volume: 144 Pages: 260-263
  • Peer Reviewed
• [Journal Article] Sustained improvement in cardiac function with persistent amyloid deposition in a patient with multiple myeloma-associated cardiac amyloidosis treated with bortezomib (2010)
  • Author(s): Tamaki H, Naito Y, Lee-Kawabata M, Taniguchi Y, Hao H, Hirota S, Hasegawa S, Masuyama T, Ogawa H.
  • Journal Title: Int J Hematol. Volume: 92 Pages: 655-658
  • Peer Reviewed
• [Journal Article] Iron Regulatory Hormone Hepcidin Decreases in Chronic Heart Failure Patients With Anemia (2010)
  • Author(s): Matsumoto M, Tsujino T, Lee-Kawabata M, Naito Y, Akahori H, Sakoda T, Ohyanagi M, Tomosugi N, Masuyama T.
  • Journal Title: Circ J. Volume: 74 Pages: 301-306
  • Peer Reviewed
• [Journal Article] Serum interleukin-6 and C-reactive protein are markedly elevated in acute decompensated heart failure patients with left ventricular systolic dysfunction (2010)
  • Author(s): Matsumoto M, Tsujino T, Lee-Kawabata M, Naito Y, Sakoda T, Ohyanagi M, Masuyama T.
  • Journal Title: Cytokine. Volume: 49 Pages: 264-268
  • Peer Reviewed
• [Presentation] 慢性腎臓病モデルにおける鉄の関与 (2011)
  • Author(s): 藤井彩, 内藤由朗, 澤田悠, 辻野健, 佐々木尚子, 赤堀宏州, 大柳光正, 増山理
  • Organizer: 第34回日本高血圧学会総会
  • Place of Presentation: 栃木
  • Year and Date: 20111020-22
• [Presentation] 大動脈弁狭窄症弁組織におけるBone morphogenetic protein-binding endothelial regulator(BMPER)発現 (2011)
  • Author(s): 澤田悠, 内藤由朗, 辻野健, 奥原祥貴, 江口明世, 岩破俊博, 赤堀宏州, 廣谷信一, 大柳光正, 光野正孝, 宮本裕治, 増山理
  • Organizer: 第59回日本心臓病学会学術集会
  • Place of Presentation: 神戸
  • Year and Date: 20110923-25
• [Presentation] Altered expression of iron regulating system in heart failure model rats : a possible mechanism of anemia associated with heart failure (2011)
  • Author(s): Naito Y, Tsujino T, Sawada H, Eguchi A, Iwasaku T, Akahori H, Hirotani S, Ohyanagi M, Masuyama T.
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Place of Presentation: 横浜
  • Year and Date: 20110803-04
• [Book] エリスロポエチン.循環器Circulation島本和明総編、筒井裕之編 (2012)
  • Author(s): 内藤由朗、増山理
  • Total Pages: 122-131
  • Publisher: 医学出版
• [Book] 心腎連関と貧血. Cardiovascular Frontier (2012)
  • Author(s): 内藤由朗、増山理
  • Total Pages: 24-29
  • Publisher: メディカルレビュー社
• [Book] 心不全における貧血・循環器臨床サピアCKDと心血管病を理解する-診療に活かすためのステップアップ;永井良三総編、筒井裕之編 (2010)
  • Author(s): 内藤由朗、増山理
  • Total Pages: 179-181
  • Publisher: 中山書店