Feto-maternal network on pregnancy-induced hypertension

2009 Fiscal Year Final Research Report

• Project/Area Number: 17108004
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Research Field: Applied molecular and cellular biology
• Research Institution: University of Tsukuba
• Principal Investigator: FUKAMIZU Akiyoshi University of Tsukuba, 大学院・生命環境科学研究科, 教授 (60199172)
• Co-Investigator(Kenkyū-buntansha): TANIMOTO Keiji 筑波大学, 大学院・生命環境科学研究科, 准教授 (90261776) ; KAKOU Kouichirou 筑波大学, 大学院・生命環境科学研究科, 講師 (60311594) ; ISHIDA Junji 筑波大学, 大学院・生命環境科学研究科, 講師 (30323257) ; DAITOKU Hiroaki 筑波大学, 大学院・生命環境科学研究科, 講師 (30361314)
• Project Period (FY): 2005 – 2009
• Keywords: 妊娠中毒症 / 妊娠高血圧症候群 / 母胎間ネットワーク / レニン-アンジオテンシン系 / 子宮内発育遅延 / トランスジェニックマウス / アペリン-APJ受容体 / 胎児-胎盤系

Research Abstract

In the present study, using the model mice associated with hypertension during pregnancy (PAH) developed in our laboratory, we have investigated (1) the pathogenesis of pregnancy-associated hypertension and the feto-maternal network, (2) the development of intrauterine growth retardation (IUGR) and its molecular mechanism, and (3) the possible involvement of a new cardiovascular system, APJ, in the pathogenesis of hypertension during pregnancy. In PAH mice, the dysfunction of endothelial cells in the placenta as the core of feto-maternal network known to play an integral part of pregnancy was observed, suggesting the development of IUGR.All pups associated with IUGR born from hypertensive mothers showed cardiac hypertrophy, anemia like phenotypes, and atrophy of many organs other than the heart, and died one day after birth. Furthermore, PAH mice showed the similar phenotypes to human HELLP syndrome. Moreover, it was suggested that APJ was involved in the exacerbation of proteinuria induced in PAH mice at the late pregnancy.

Research Products

• [Journal Article] Activation of renin-angiotensin system induces osteoporosis independently of hypertension (2009)
  • Author(s): Asaba Y, Ito M, Fumoto T, Watanabe K, Fukuhara R, Takeshita S, Nimura Y, Ishida J, Fukamizu A, Ikeda K.
  • Journal Title: J.Bone Miner.Res. 24 Pages: 241-250
  • Peer Reviewed
• [Journal Article] Reduced angiogenesis and delay in wound healing in angiotensin II type 1a receptor-deficient mice (2009)
  • Author(s): Kurosaka M, Suzuki T, Hosono K, Kamata Y, Fukamizu A, Kitasato H, Fujita Y, Majima M.
  • Journal Title: Biomed.Pharmacother. 63 Pages: 627-634
  • Peer Reviewed
• [Journal Article] (Pro)renin receptor-mediated signal transduction and tissue renin-angiotensin system contribute to diabetes-induced retinal inflammation (2009)
  • Author(s): Satofuka S, Ichihara A, Nagai N, Noda K, Ozawa Y, Fukamizu A, Tsubota K, Itoh H, Oike Y, Ishida S.
  • Journal Title: Diabetes 58 Pages: 1625-1633
  • Peer Reviewed
• [Journal Article] (Pro)renin receptor promotes choroidal neovascularization by activating its signal transduction and tissue renin-angiotensin system (2008)
  • Author(s): Satofuka S, Ichihara A, Nagai N, Noda K, Ozawa Y, Fukamizu A, Tsubota K, Itoh H, Oike Y, Ishida S.
  • Journal Title: Am.J.Pathol. 173 Pages: 1911-198
  • Peer Reviewed
• [Journal Article] Angiotensin type 1 receptor blockade prevents cardiac remodeling in mice with pregnancy-associated hypertension (2008)
  • Author(s): Sakairi A, Ishida J, Honjo K, Inaba S, Nakamura S, Sugiyama F, Yagami K, Fukamizu A.
  • Journal Title: Hypertens.Res. 31 Pages: 2165-2175
  • Peer Reviewed
• [Journal Article] A combination of HNF-4 and Foxo1 is required for reciprocal transcriptional regulation of glucokinase and glucose-6-phosphatase genes in response to fasting and feeding (2008)
  • Author(s): Hirota K, Sakamaki JI, Ishida J, Shimamoto Y, Nishihara S, Kodama N, Ohta K, Yamamoto M, Tanimoto K, Fukamizu A.
  • Journal Title: J.Biol.Chem. 283 Pages: 32432-32441
  • Peer Reviewed
• [Journal Article] Evaluation of novel cyclic analogues of apelin (2008)
  • Author(s): Hamada J, Kimura J, Ishida J, Kohda T, Morishita S, Ichihara S, Fukamizu A.
  • Journal Title: Int.J.Mol.Med. 22 Pages: 547-552
  • Peer Reviewed
• [Journal Article] Inhibitory effects of benzyl benzoate and its derivatives on angiotensin II-induced hypertension (2008)
  • Author(s): Ohno O, Ye M, Koyama T, Yazawa K, Mura E, Matsumoto H, Ichino T, Yamada K, Nakamura K, Ohno T, Yamaguchi K, Ishida J, Fukamizu A, Uemura D.
  • Journal Title: Bioorg.Med.Chem. 16 Pages: 7843-7852
  • Peer Reviewed
• [Journal Article] Deterioration of atherosclerosis in mice lacking angiotensin II type 1A receptor in bone marrow-derived cells (2008)
  • Author(s): Kato H, Ishida J, Nagano K, Honjo K, Sugaya T, Takeda N, Sugiyama F, Yagami K, Fujita T, Nangaku M, Fukamizu A.
  • Journal Title: Lab.Invest. 88 Pages: 731-739
  • Peer Reviewed
• [Journal Article] Renin inhibition reduces hypercholesterolemia-induced atherosclerosis in mice (2008)
  • Author(s): Lu H, Rateri DL, Feldman DL, Jr RJ, Fukamizu A, Ishida J, Oesterling EG, Cassis LA, Daugherty A.
  • Journal Title: J.Clin.Invest. 118 Pages: 984-993
  • Peer Reviewed
• [Journal Article] Impaired placental neovascularization in mice with pregnancy-associated hypertension (2008)
  • Author(s): Furuya M, Ishida J, Inaba S, Kasuya Y, Kimura S, Nemori R, Fukamizu A.
  • Journal Title: Lab.Invest. 88 Pages: 416-429
  • Peer Reviewed
• [Journal Article] Angiotensin II regulates liver regeneration via type 1 receptor following partial hepatectomy in mice (2008)
  • Author(s): Yayama K, Miyagi R, Sugiyama K, Sugaya T, Fukamizu A, Okamoto H.
  • Journal Title: Biol.Pharm.Bull. 31 Pages: 1356-1361
  • Peer Reviewed
• [Journal Article] A single nucleotide mutation in the mouse renin promoter disrupts blood pressure regulation (2008)
  • Author(s): Tanimoto K, Sugiura A, Kanafusa S, Saito T, Masui N, Yanai K, Fukamizu A.
  • Journal Title: J.Clin.Invest. 118 Pages: 1006-1016
  • Peer Reviewed
• [Journal Article] Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt (2008)
  • Author(s): Yamagata K, Daitoku H, Takahashi Y, Namiki K, Hisatake K, Kako K, Mukai H, Kasuya Y, Fukamizu A.
  • Journal Title: Mol.Cell 32 Pages: 221-231
  • Peer Reviewed
• [Journal Article] Pathophysiology of placentation abnormalities in pregnancy-induced hypertension (2008)
  • Author(s): Furuya M, Ishida J, Aoki I, Fukamizu A.
  • Journal Title: Vasc.Health Risk Manag. 4 Pages: 1301-1313
  • Peer Reviewed
• [Journal Article] Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis (2007)
  • Author(s): Hashimoto T, Kihara M, Imai N, Yoshida S, Shimoyamada H, Yasuzaki H, Ishida J, Toya Y, Kiuchi Y, Hirawa N, Tamura K, Yazawa T, Kitamura H, Fukamizu A, Umemura S.
  • Journal Title: Am.J.Pathol. 171 Pages: 1705-1712
  • Peer Reviewed
• [Journal Article] Apelin stimulates myosin light chain phosphorylation in vascular smooth muscle cells (2006)
  • Author(s): Hashimoto T, Kihara M, Ishida J, Imai N, Yoshida S, Toya Y, Fukamizu A, Kitamura H, Umemura S.
  • Journal Title: Arterioscler.Thromb.Vasc.Biol. 26 Pages: 1267-1672
  • Peer Reviewed
• [Journal Article] Expression of cyclooxygenase-2 in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice (2006)
  • Author(s): Hashimoto T, Kihara M, Sato K, Matsushita K, Tanimoto K, Toya Y, Fukamizu A, Umemura S.
  • Journal Title: Nephron Physiol 102 Pages: 1-8
  • Peer Reviewed
• [Journal Article] Enhanced erythropoiesis mediated by activation of the renin-angiotensin system via angiotensin II type 1a receptor (2005)
  • Author(s): Kato H, Ishida J, Imagawa S, Saito T, Suzuki N, Matsuoka T, Sugaya T, Tanimoto K, Yokoo T, Ohneda O, Sugiyama F, Yagami K, Fujita T, Yamamoto M, Nangaku M, Fukamizu A.
  • Journal Title: FASEB J. 19 Pages: 2023-2025
  • Peer Reviewed
• [Journal Article] Angiotensin-converting enzyme 2 protects from severe acute lung failure (2005)
  • Author(s): Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, Yang P, Sarao R, Wada T, Leong-Poi H, Crackower MA, Fukamizu A, Hui CC, Hein L, Uhlig S, Slutsky AS, Jiang C, Penninger JM.
  • Journal Title: Nature 436 Pages: 112-116
  • Peer Reviewed
• [Journal Article] G protein-coupled APJ receptor signaling induces focal adhesion formation and cell motility (2005)
  • Author(s): Hashimoto Y, Ishida J, Yamamoto R, Fujiwara K, Asada S, Kasuya Y, Mochizuki N, Fukamizu A.
  • Journal Title: Int.J.Mol.Med. 16 Pages: 787-792
  • Peer Reviewed
• [Journal Article] Identification of cis-regulatory sequences in the human angiotensinogen gene by transgene coplacement and site-specific recombination (2005)
  • Author(s): Shimizu T, Oishi T, Omori A, Sugiura A, Hirota K, Aoyama H, Saito T, Sugaya T, Kon Y, Engel JD, Fukamizu A, Tanimoto K.
  • Journal Title: Mol.Cell.Biol. 25 Pages: 2938-2945
  • Peer Reviewed
• [Journal Article] Attenuation of diet-induced weight gain and adiposity through increased energy expenditure in mice lacking angiotensin II type 1a receptor (2005)
  • Author(s): Kouyama R, Suganami T, Nishida J, Tanaka M, Toyoda T, Kiso M, Chiwata T, Miyamoto Y, Yoshimasa Y, Fukamizu A, Horiuchi M, Hirata Y, Ogawa Y.
  • Journal Title: Endocrinology 146 Pages: 3481-3489
  • Peer Reviewed
• [Journal Article] Differential roles of renin and angiotensinogen in the feto-maternal interface in the development of complications of pregnancy (2005)
  • Author(s): Takimoto-Ohnishi E, Saito T, Ishida J, Ohnishi J, Sugiyama F, Yagami K, Fukamizu A.
  • Journal Title: Mol.Endocrinol. 19 Pages: 1361-1372
  • Peer Reviewed
• [Presentation] 妊娠高血圧症モデルマウスにおける胎盤の血管構造変化に関する研究 (2009)
  • Author(s): 石田純治, 古屋充子, 稲葉早希, 粕谷善俊, 木村定雄, 根守良一, 深水昭吉
  • Organizer: 第30回 日本妊娠高血圧学会
  • Place of Presentation: 岡山
  • Year and Date: 2009-08-29
• [Presentation] 妊娠高血圧マウスの心臓リモデリングに対するAT1シグナル阻害の改善効果 (2009)
  • Author(s): 中村匠子, 石田純治, 坂入旭, 本城花織, 稲葉早希, 杉山文博, 八神健一, 深水昭吉
  • Organizer: 第30回 日本妊娠高血圧学会
  • Place of Presentation: 岡山
  • Year and Date: 2009-08-29
• [Presentation] 妊娠高血圧症候群における血管新生の病態解析 (2008)
  • Author(s): 古屋充子, 石田純治, 武内利直, 碓井宏和, 中谷行雄, 深水昭吉
  • Organizer: 第97回 日本病理学会
  • Place of Presentation: 石川
  • Year and Date: 2008-05-15
• [Remarks] ホームページ等
  • URL: http://akif2.tara.tsukuba.ac.jp/