Development of the high blood pressure medical treatment by angiotensin receptor binding molecule

• Project/Area Number: 24790950
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Endocrinology
• Research Institution: Yokohama City University
• Principal Investigator: WAKUI Hiromichi 横浜市立大学, 附属病院, 助教 (10587330)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: レニンアンジオテンシン / 受容体 / 高血圧 / 動脈硬化 / 尿細管 / アンジオテンシン / レニンーアンジオテンシン系 / 腎尿細管

Research Abstract

We paid our attention to the functional role of renal tubule ATRAP in vivo, and, using renal tubule ATRAP overexpression transgenic mice, we examined functional role of renal tubule ATRAP in blood pressure regulation in response to pathologic stimulation. As a result, while ATRAP, with a high endogenous expression in renal tubules, preserves baseline physiological AT1R signaling activity, it would suppress pathological overactivation of AT1R signaling under pathological conditions. Furthermore, using vascular ATRAP overexpression transgenic mouse, we demonstrated that vascular ATRAP can suppress oxidative stress at local tissue sites and inhibit arteriosclerosis under pathological conditions.

Research Products

• [Journal Article] Effects of Ang II receptor blocker irbesartan on adipose tissue function in mice with metabolic disorders. (2014)
  • Author(s): Maeda A, Tamura K, Wakui H, Ohsawa M, Azushima K, Uneda K, Kobayashi R, Tsurumi-Ikeya Y, Kanaoka T, Dejima T, Ohki K, Haku S, Yamashita A, Umemura S.
  • Journal Title: Int J Med Sci. Volume: 11(6) Issue: 6 Pages: 646-51
  • DOI: 10.7150/ijms.8577
  • Peer Reviewed / Open Access
• [Journal Article] Endovascular treatment of renal artery stenosis improves contralateral renal hypertrophy with nephrotic syndrome. (2014)
  • Author(s): Wakui H, Hosokawa Y, Oshikawa J, Tamura K, Toya Y, Yabana M, Furihata S, Sugano T, Umemura S.
  • Journal Title: CEN Case Rep. Volume: 3 Issue: 1 Pages: 53-55
  • DOI: 10.1007/s13730-013-0085-y
  • Peer Reviewed
• [Journal Article] Activation of angiotensin II type 1 receptor-associated protein exerts an inhibitory effect on vascular hypertrophy and oxidative stress in angiotensin II-mediated hypertension. (2013)
  • Author(s): Wakui H, Dejima T, Tamura K, Uneda K, Azuma K, Maeda A, Ohsawa M, Kanaoka T, Azushima K, Kobayashi R, Matsuda M, Yamashita A, Umemura S.
  • Journal Title: Cardiovasc Res. Volume: 100(3) Issue: 3 Pages: 511-9
  • DOI: 10.1093/cvr/cvt225
  • Peer Reviewed / Open Access
• [Journal Article] Bofu-tsu-shosan, an oriental herbal medicine, exerts a combinatorial favorable metabolic modulation including antihypertensive effect on a mouse model of human metabolic disorders with visceral obesity. (2013)
  • Author(s): Azushima K, Tamura K, Wakui H, Maeda A, Ohsawa M, Uneda K, Kobayashi R, Kanaoka T, Dejima T, Fujikawa T, Yamashita A, Toya Y, Umemura S.
  • Journal Title: PLoS One. Volume: 8(10) Issue: 10 Pages: e75560-e75560
  • DOI: 10.1371/journal.pone.0075560
  • Peer Reviewed / Open Access
• [Journal Article] Angiotensin receptor-binding protein ATRAP/Agtrap inhibits metabolic dysfunction with visceral obesity. (2013)
  • Author(s): Maeda A, Tamura K, Wakui H, Dejima T, Ohsawa M, Azushima K, Kanaoka T, Uneda K, Matsuda M, Yamashita A, Miyazaki N, Yatsu K, Hirawa N, Toya Y, Umemura S.
  • Journal Title: J Am Heart Assoc. Volume: 2(4) Issue: 4
  • DOI: 10.1161/jaha.113.000312
  • Peer Reviewed / Open Access
• [Journal Article] Addition of aliskiren to Angiotensin receptor blocker improves ambulatory blood pressure profile and cardiorenal function better than addition of benazepril in chronic kidney disease (2013)
  • Author(s): Ohsawa M, Wakui H, et al
  • Journal Title: Int J Mol Sci Volume: 14(8) Issue: 8 Pages: 15361-75
  • DOI: 10.3390/ijms140815361
  • Peer Reviewed
• [Journal Article] Upstream stimulatory factors 1 and 2 mediate the transcription of angiotensin II binding and inhibitory protein. (2013)
  • Author(s): Matsuda M, Tamura K, Wakui H, Maeda A, Ohsawa M, Kanaoka T, Azushima K, Uneda K, Haku S, Tsurumi-Ikeya Y, Toya Y, Maeshima Y, Yamashita A, Umemura S.
  • Journal Title: J Biol Chem. Volume: 288(26) Issue: 26 Pages: 19238-49
  • DOI: 10.1074/jbc.m113.451054
  • Peer Reviewed / Open Access
• [Journal Article] Therapeutic potential of low-density lipoprotein apheresis in the management of peripheral artery disease in patients with chronic kidney disease (2013)
  • Author(s): Tamura K, Wakui H, et al
  • Journal Title: Ther Apher Dial Volume: 17(2) Pages: 185-92
• [Journal Article] Enhanced angiotensin receptor-associated protein in renal tubule suppresses angiotensin-dependent hypertension. (2013)
  • Author(s): Wakui H, Tamura K, Masuda S, Tsurumi-Ikeya Y, Fujita M, Maeda A, Ohsawa M, Azushima K, Uneda K, Matsuda M, Kitamura K, Uchida S, Toya Y, Kobori H, Nagahama K, Yamashita A, Umemura S.
  • Journal Title: Hypertension. Volume: 61(6) Issue: 6 Pages: 1203-10
  • DOI: 10.1161/hypertensionaha.111.00572
  • Peer Reviewed / Open Access
• [Journal Article] The angiotensin II type 1 receptor blocker olmesartan preferentially improves nocturnal hypertension and proteinuria in chronic kidney disease (2013)
  • Author(s): Yanagi M, Wakui H, et al
  • Journal Title: Hypertens Res Volume: 36(3) Issue: 3 Pages: 262-9
  • DOI: 10.1038/hr.2012.184
  • Peer Reviewed
• [Journal Article] Effects of aliskiren-based therapy on ambulatory blood pressure profile, central hemodynamics, and arterial stiffness in nondiabetic mild to moderate hypertensive patients (2012)
  • Author(s): Kanaoka T, Wakui H, et al
  • Journal Title: J Clin Hypertens (Greenwich) Volume: 14(8) Pages: 522-9
  • Peer Reviewed
• [Journal Article] Relationship of Ambulatory Blood Pressure and the Heart Rate Profile with Renal Function Parameters in Hypertensive Patients with Chronic Kidney Disease (2012)
  • Author(s): Kanaoka T, Tamura K, et al.
  • Journal Title: Clinical and Experimental Hypertension Volume: 34 Issue: 4 Pages: 264-269
  • DOI: 10.3109/10641963.2012.681082
  • Peer Reviewed
• [Journal Article] Mice Lacking Hypertension Candidate Gene ATP2B1 in Vascular Smooth Muscle Cells show Significant Blood Pressure Elevation. (2012)
  • Author(s): Kobayashi Y, et al.
  • Journal Title: Hypertension. Volume: 59 Issue: 4 Pages: 854-860
  • DOI: 10.1161/hypertensionaha.110.165068
  • Peer Reviewed
• [Presentation] Cardiovascular enhancement of angiotensin II type 1 receptor-associated protein ameliorates vascular lesion development in angiotensin II-induced hypertension. (2014)
  • Author(s): Wakui H, Tamura K, Dejima T, Ohsawa M, Azushima K, Uneda K, Kobayashi R, Ikeya Y, Toya Y, Umemura S.
  • Organizer: 第18回国際血管生物学会
  • Place of Presentation: みやこめっせ（京都府）
• [Presentation] Angiotensin receptor-binding protein ATRAP in renal tubule is an important modulator of blood pressure under pathological stimulation. (2014)
  • Author(s): Wakui H, Tamura K, Ohsawa M, Kobayashi R, Uneda K, Azushima K, Toya Y, Umemura S．
  • Organizer: 第14回アジア太平洋腎臓学会議
  • Place of Presentation: 品川プリンスホテル（東京都）
• [Presentation] ENHANCEMENT OF ANGIOTENSIN II TYPE 1 RECEPTOR ASSOCIATED PROTEIN SUPPRESSES VASCULAR REMODELING AND OXIDATIVE STRESS IN ANGIOTENSIN II-MEDIATED HYPERTENSION. (2014)
  • Author(s): Wakui H, Tamura K, Kobayashi R, Uneda K, Azushima K, Ohsawa M, Dejima T, Ikeya Y, Kanaoka T, Maeda A, Ishigami T, Hirawa N, Yabana M, Toya Y, Umemura S.
  • Organizer: 第25回国際高血圧学会/第24回欧州高血圧学会
  • Place of Presentation: アテネ，ギリシャ
• [Presentation] Enhanced Angiotensin Receptor-Associated Protein in Renal Tubule Suppresses Angiotensin-Dependent Hypertension (2013)
  • Author(s): 涌井広道
  • Organizer: 第36回日本高血圧学会総会
  • Place of Presentation: 大阪
  • Year and Date: 2013-10-24
• [Presentation] Enhanced AT1 receptor-associated protein in renal tubule suppresses angiotensin-mediated hypertension (2013)
  • Author(s): Wakui H
  • Organizer: 第50回ヨーロッパ腎臓・透析・移植学会
  • Place of Presentation: イスタンブール
  • Year and Date: 2013-05-20
• [Presentation] ENHANCED AT1 RECEPTOR-ASSOCIATED PROTEIN IN RENAL TUBULE SUPPRESSES ANGIOTENSIN-MEDIATED HYPERTENSION (2013)
  • Author(s): Hiromichi Wakui
  • Organizer: ERA-EDTA 50th congress
  • Place of Presentation: イスタンブール，トルコ
• [Presentation] Enhanced AT1 receptor-associated protein in the distal nephron suppresses angiotensin dependent hypertension (2012)
  • Author(s): Wakui H
  • Organizer: 24th Scientific Meeting of the International Society of Hypertension
  • Place of Presentation: Sydney
  • Year and Date: 2012-10-01
• [Presentation] 尿細管におけるアンジオテンシン受容体結合因子の発現量増加はアンジオテンシンII 依存性高血圧を抑制する (2012)
  • Author(s): 涌井広道
  • Organizer: 第35回日本高血圧学会総会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-09-20
• [Presentation] 尿細管におけるアンジオテンシン受容体結合因子の発現量増加はアンジオテンシンII 依存性高血圧を抑制する (2012)
  • Author(s): 涌井広道
  • Organizer: 第3回Front-J 研究会
  • Place of Presentation: 品川
  • Year and Date: 2012-08-10
• [Remarks] 涌井助教、田村准教授らの研究成果がHypertension誌に論文掲載されました！
  • URL: http://www.yokohama-cu.ac.jp/amedrc/res/k.tamura_2013_05.html
• [Remarks] 涌井助教が日本高血圧学会Young Investigator’s Award優秀賞を受賞しました!
  • URL: http://www.yokohama-cu.ac.jp/amedrc/res/wakui_2013_10.html