Role of androgen receptor in sex dependent and independent manner

• Project/Area Number: 25461389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Endocrinology
• Research Institution: The University of Tokushima
• Principal Investigator: AIHARA Ken-ichi 徳島大学, 大学院医歯薬学研究部, 特任教授 (70372711)
• Co-Investigator(Kenkyū-buntansha): IKEDA Yasumasa 徳島大学, 大学院医歯薬学研究部, 准教授 (60432754) ; YAGI Shusuke 徳島大学, 大学院医歯薬学研究部, 助教 (00507650)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アンドロゲン受容体 / アンジオテンシンII / ApoE / 心筋肥大 / 動脈硬化 / マクロファージ / ノックアウトマウス / 性差 / 心血管病

Outline of Final Research Achievements

Not only menopause but also andropause are critical issue to prevent the development of cardiovascular diseases in elderly people. In order to clarify the physiological role of androgen receptor (AR) in the process of cardiovascular remodeling, we studied mouse models of angiotensin II-infused female AR-deficient mice and macrophage-specific male AR-deficient mice. The values of cardiac hypertrophy and left ventricular interstitial fibrosis area showed no difference between the angiotensin II-infused female AR-deficient mice and wild type mice. In contrast, aortic adventitia hyperplasia was attenuated in AR-deficient female mice. In addition, macrophage specific AR-deficient male mice did not show the acceleration of atherosclerotic plaque area. Therefore, AR in macrophage was not associated with the development of atherosclerosis.

Research Products

• [Journal Article] Roles of the Androgen – Androgen Receptor System in Vascular Angiogenesis (2016)
  • Author(s): Sumiko Yoshida, Yasumasa Ikeda and Ken-ichi Aihara
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 23 Issue: 3 Pages: 257-265
  • DOI: 10.5551/jat.31047
  • NAID: 130005131882
  • ISSN: 1340-3478, 1880-3873
  • Peer Reviewed / Open Access
• [Journal Article] Serum carboxy-terminal telopeptide of type I collagen levels are associated with carotid atherosclerosis in patients with cardiovascular risk factors (2016)
  • Author(s): Kondo T, Endo I, Aihara K, Onishi Y, Dong B, Ohguro Y, Kurahashi K, Yoshida S, Fujinaka Y, Kuroda A, Matsuhisa M, Fukumoto S, Matsumoto T, Abe M.
  • Journal Title: Endocrine Journal Volume: 63 Issue: 4 Pages: 397-404
  • DOI: 10.1507/endocrj.EJ15-0589
  • NAID: 130005146452
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Bilirubin exerts pro-angiogenic effects through an Akt-eNOS-dependent pathway (2015)
  • Author(s): Yasumasa Ikeda, Hamano Hirofumi, Satoh Akiho, Horinouchi Yuya, Yuki Izawa-Ishizawa, Yoshitaka Kihira, Keisuke Ishizawa, Ken-ichi Aihara, Koichiro Tsuchiya and Toshiaki Tamaki
  • Journal Title: Hypertension Research Volume: 38(11) Issue: 11 Pages: 733-740
  • DOI: 10.1038/hr.2015.74
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus. (2015)
  • Author(s): Yagi S, Aihara K, Akaike M, Fukuda D, Salim HM, Ishida M, Matsuura T, Ise T, Yamaguchi K, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Matsumoto T, Sata M.
  • Journal Title: Diabetes Metab J. Volume: 39 Issue: 4 Pages: 342-347
  • DOI: 10.4093/dmj.2015.39.4.342
  • Peer Reviewed / Open Access
• [Journal Article] Non-invasive Measurement of Skin Autofluorescence as a Beneficial Surrogate Marker for Atherosclerosis in Patients with Type 2 Diabetes (2015)
  • Author(s): Temma J, Matsuhisa M, Horie T, Kuroda A, Mori H, Tamaki M, Endo I, Aihara K, Abe M, Matsumoto T.
  • Journal Title: The Journal of Medical Investigation Volume: 62 Issue: 3.4 Pages: 126-129
  • DOI: 10.2152/jmi.62.126
  • NAID: 130005099157
  • ISSN: 1343-1420, 1349-6867
  • Peer Reviewed / Open Access
• [Journal Article] Reduced ratio of eicosapentaenoic acid and docosahexaenoic acid to arachidonic acid is associated with early onset of acute coronary syndrome (2015)
  • Author(s): Yagi S, Aihara K, Fukuda D, Takashima A, Bando M, Hara T, Nishimoto S, Ise T, Kusunose K, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  • Journal Title: Nut J Volume: 14 Issue: 1 Pages: 111-111
  • DOI: 10.1186/s12937-015-0102-4
  • Peer Reviewed / Open Access
• [Journal Article] Factor VII Tokushima: the first case of factor VII Cys22Gly with the development of myocardial infarction in the proband receiving recombinant factor VIIa replacement therapy. (2015)
  • Author(s): Shigekiyo T, Sekimoto E, Shibata H, Ozaki S, Okumura T, Fujinaga H, Shibata H, Aihara K, Akaike M.
  • Journal Title: Blood Coagul Fibrinolysis. Volume: 26 Pages: 956-958
  • Peer Reviewed
• [Journal Article] Effects of docosahexaenoic acid on the endothelial function in patients with coronary artery disease. (2015)
  • Author(s): Yagi S, Aihara K, Fukuda D, Takashima A, Hara T, Hotchi J, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  • Journal Title: J Atheroscler Thromb. Volume: 22 Pages: 447-454
  • NAID: 130004700298
  • Peer Reviewed / Open Access
• [Journal Article] Effect of combination tablets containing amlodipine 10 mg and irbesartan 100 mg on blood pressure and cardiovascular risk factors in patients with hypertension. (2014)
  • Author(s): Yagi S, Takashima A, Mitsugi M, Wada T, Hotchi J, Aihara K, Hara T, Ishida M, Fukuda D, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  • Journal Title: Ther Clin Risk Manag. Volume: 11 Pages: 83-88
  • DOI: 10.2147/tcrm.s72299
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Serum concentration of eicosapentaenoic acid is associated with cognitive function in patients with coronary artery disease. (2014)
  • Author(s): Yagi S, Hara T, Ueno R, Aihara K, Fukuda D, Takashima A, Hotchi J, Ise T, Yamaguchi K, Tobiume T, Iwase T, Yamada H, Soeki T, Wakatsuki T, Shimabukuro M, Akaike M, Sata M.
  • Journal Title: Nutr J. Volume: 13 Issue: 1 Pages: 112-112
  • DOI: 10.1186/1475-2891-13-112
  • Peer Reviewed / Open Access
• [Journal Article] Anti-albuminuric effect of the aldosterone blocker eplerenone in non-diabetic hypertensive patients with albuminuria: a double-blind, randomised, placebo-controlled trial. (2014)
  • Author(s): Ando K, Ohtsu H, Uchida S, Kaname S, Arakawa Y, Fujita T; EVALUATE Study Group (including Aihara K).
  • Journal Title: Lancet Diabetes Endocrinol. Volume: 12 Pages: 944-953
  • Peer Reviewed
• [Journal Article] High serum parathyroid hormone and calcium are risk factors for hypertension in Japanese patients. (2014)
  • Author(s): Yagi S, Aihara K, Kondo T, Endo I, Hotchi J, Ise T, Iwase T, Akaike M, Matsumoto T, Sata M.
  • Journal Title: Endocr J. Volume: 61 Pages: 477-481
  • NAID: 130004443979
  • Peer Reviewed / Open Access
• [Journal Article] Diabetic conditions differentially affect the endothelial function, arterial stiffness and carotid atherosclerosis. (2014)
  • Author(s): Kinouchi M, Aihara KI, Fujinaka Y, Yoshida S, Ooguro Y, Kurahashi K, Kondo T, Aki N, Kuroda A, Endo I, Matsuhisa M, Matsumoto T.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 21 Pages: 486-500
  • Peer Reviewed
• [Journal Article] Androgen receptor promotes sex-independent angiogenesis in response to ischemia and is required for activation of vascular endothelial growth factor receptor signaling (2013)
  • Author(s): Yoshida S, Aihara K, Ikeda Y, Sumitomo-Ueda Y, Uemoto R, Ishikawa K, Ise T, Yagi S, Iwase T, Mouri Y, Sakari M, Matsumoto T, Takeyama K, Akaike M, Matsumoto M, Sata M, Walsh K, Kato S, Matsumoto T.
  • Journal Title: Circulation Volume: 128 Issue: 1 Pages: 60-71
  • DOI: 10.1161/circulationaha.113.001533
  • Peer Reviewed
• [Presentation] 2型糖尿病患者の左室形態および機能における強化インスリン療法の効果 (2015)
  • Author(s): 粟飯原賢一、 吉田守美子、 森本佳奈、 倉橋清衛、 近藤剛史、田蒔基行、 黒田暁生、 明比祐子、 遠藤逸朗、 船木真理、福本誠二、 松久宗英、 安倍正博
  • Organizer: 日本糖尿病学会第53回中国四国地方会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2015-10-31
• [Presentation] 長期のアンジオテンシンII受容体拮抗薬基盤高血圧治療による心筋リモデリングおよび頸動脈硬化症への効果検証 (2015)
  • Author(s): 粟飯原賢一、吉田守美子、森本佳奈、倉橋清衛、田蒔基行、近藤剛史、黒田暁生、遠藤逸朗、松久宗英、安倍正博
  • Organizer: 第38日本高血圧学会総会
  • Place of Presentation: 愛媛県県民文化会館（愛媛県松山市）
  • Year and Date: 2015-10-10
• [Presentation] 2型糖尿病患者の減塩療法による血圧低下に関連する因子の解析 (2015)
  • Author(s): 加藤正樹、森本佳奈、粟飯原賢一、吉田守美子、倉橋清衛、田蒔基行、近藤剛史、黒田暁生、遠藤逸朗、松久宗英、福本誠二、安倍正博
  • Organizer: 第15回日本内分泌学会四国支部学術集会
  • Place of Presentation: 高知大学医学部キャンパス（高知県南国市）
  • Year and Date: 2015-09-05
• [Presentation] 内因性血清尿酸値およびフェブキソスタットによる頸動脈硬化への影響 (2015)
  • Author(s): 粟飯原賢一、吉田守美子、上元良子、石川カズ江、松本俊夫、安倍正博
  • Organizer: 第47回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 仙台国際センター・新展示施設（宮城県仙台市）
  • Year and Date: 2015-07-10
• [Presentation] ARB基盤高血圧治療の長期心腎保護効果における糖尿病の影響 (2015)
  • Author(s): 粟飯原賢一、吉田守美子、大黒由加里、田蒔 基行、近藤剛史、倉橋清衛、黒田暁生、遠藤逸朗、松久宗英、松本俊夫
  • Organizer: 第58回総会日本糖尿病学会年次学術集会
  • Place of Presentation: 海峡メッセ下関(山口県下関市)
  • Year and Date: 2015-05-22
• [Presentation] 本態性高血圧患者におけるアンジオテンシンII 受容体拮抗薬単独およびカルシウム拮抗薬併用 による長期心筋保護効果の検証 (2015)
  • Author(s): 粟飯原賢一、吉田守美子、大黒由加里、倉橋清衛、近藤剛史、田蒔基行、黒田暁生、遠藤逸朗、松久宗英、松本俊夫
  • Organizer: 第88回日本内分泌学会学術総会
  • Place of Presentation: ホテルニューオータニ東京（東京都千代田区）
  • Year and Date: 2015-04-25
• [Presentation] アンジオテンシン受容体拮抗薬および カルシウム拮抗薬併用による心筋 リモデリング抑制の長期効果 (2014)
  • Author(s): 粟飯原賢一、吉田守美子、大黒由加里、倉橋清衛、近藤剛史、遠藤逸朗、松本俊夫
  • Organizer: 第37回日本高血圧学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-10-18
• [Presentation] 動脈硬化および虚血に対するeNOS非依存的なピタバスタチンの臓器保護効果の検討 (2014)
  • Author(s): 粟飯原賢一、吉田守美子、池田康将、上元良子、石川カズ江、赤池雅史、松本俊夫
  • Organizer: 第46回日本動脈硬化学会 総会・学術集会
  • Place of Presentation: 京王プラザホテル（東京都新宿区）
  • Year and Date: 2014-07-11
• [Presentation] 生活習慣病治療薬が血管内皮機能 に及ぼす影響の検証 (2014)
  • Author(s): 粟飯原賢一、木内美瑞穂、大黒由加里、倉橋清衛、近藤剛史、安藝菜奈子、黒田暁生、遠藤逸朗、松久宗英、松本俊夫
  • Organizer: 第111回日本内科学会講演会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
  • Year and Date: 2014-04-12
• [Presentation] 心血管システム恒常性維持における アンドロゲン受容体の意義 (2013)
  • Author(s): 粟飯原賢一
  • Organizer: 文部科学省科学研究費補助金 新学術領域研究「性差構築の分子基盤」第5回領域会議
  • Place of Presentation: 国民宿舎 虹の松原ホテル (佐賀県)
  • Invited
• [Presentation] 心血管ストレス制御における アンドロゲン受容体機能の性差 (2013)
  • Author(s): 粟飯原賢一、吉田守美子、池田康将、上元良子、石川カズ江、松本俊夫
  • Organizer: 第4回テストステロン研究会
  • Place of Presentation: ホテルマロウド軽井沢（長野県）