Phenotypic alterations of brain microvascular endothelium in a model of Alzheimer disease

• Project/Area Number: 23590874
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General internal medicine (including Psychosomatic medicine)
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: HAYASHI Shinichiro 独立行政法人国立循環器病研究センター, 病院, 医師 (20396740)
• Co-Investigator(Kenkyū-buntansha): SATO Naoyuki 大阪大学, 医学系研究科, 寄付講座准教授 (70372612)
• Co-Investigator(Renkei-kenkyūsha): YAMAMOTO Akitsugu 長浜バイオ大学, バイオサイエンス研究科, 教授 (30174775)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: アルツハイマー病 / オートファジー / 血管内皮

Research Abstract

The cause and progression of Alzheimer disease (AD) still remains unclear. Our present findings indicate that the progression of AD might be in part driven by phenotypic alterations in neurovascular endothelium with induction of endothelial autophagy and impairment of neurovascular regeneration in diseased brain.

Research Products

• [Journal Article] Comparison of efficacy of intensive versus mild pitavastatin therapy on lipid and inflammation biomarkers in hypertensive patients with dyslipidemia (2014)
  • Author(s): Iwashima/Jesmin S et al.
  • Journal Title: PLOS ONE Volume: 9 Issue: 2 Pages: e89057-e89057
  • DOI: 10.1371/journal.pone.0089057
  • Peer Reviewed / Open Access
• [Journal Article] Trend of office and home blood pressure control in treated hypertensive patients: Changes in antihypertensive medication and salt intake (2014)
  • Author(s): Ohta Y, Hayashi S(他6名)
  • Journal Title: Clin Exp Hypertens Volume: 36 Issue: 2 Pages: 103
  • DOI: 10.3109/10641963.2014.892118
  • Peer Reviewed / Open Access
• [Journal Article] Trend of office and home blood pressure control in treated hypertensive patients (2014)
  • Author(s): Ohta Y, Hayashi S 他
  • Journal Title: Clin Exp Hypertens Volume: 36 Pages: 103-107
  • Peer Reviewed
• [Journal Article] Oxidative stress and cyclic strain mediated smad6 regulation in vascular endothelial cells correlates with autophagy induction and endothelial dysfunction (2013)
  • Author(s): Hayashi S, Matsushita H(他2名)
  • Journal Title: Stroke Volume: vol.44(supple)(WOS:000330540201654) Pages: 111-111
  • Peer Reviewed
• [Journal Article] Phenotypic alterations of brain microvascular endothelium in a murine model of Alzheimer disease (2013)
  • Author(s): Hayashi S, Sato N(他2名)
  • Journal Title: Stroke Volume: vol.44(supple)(WOS:000330540200332) Pages: 442-442
  • Peer Reviewed
• [Journal Article] Response to renal resistive index and cardiovascular and renal outcomes in essential hypertension (2013)
  • Author(s): Doi Y, Hayashi S(他7名)
  • Journal Title: Hypertension Volume: vol.61
  • URL: http://hyper.ahajournals.org/content/61/2/e23.long
• [Journal Article] Control of home blood pressure with an amlodipine-or losartan-based regimen and progression of carotid artery intima-media thickness in hypertensive patients: The HOSP substudy (2013)
  • Author(s): Ohta Y, Hayashi S(他8名)
  • Journal Title: Clin Exp Hypertens Volume: 35 Issue: 4 Pages: 279
  • DOI: 10.3109/10641963.2013.780074
  • Peer Reviewed
• [Journal Article] Effect of bezafibrate on office, home and ambulatory blood pressure in hypertensive patients with dyslipidemia (2013)
  • Author(s): Ohta Y, Hayashi S(他4名)
  • Journal Title: J Hum Hypertens Volume: 27 Issue: 7 Pages: 417
  • DOI: 10.1038/jhh.2012.64
  • Peer Reviewed
• [Journal Article] Increased blood-brain barrier vulnerability to systemic inflammation in an Alzheimer disease mouse model (2013)
  • Author(s): Takeda S, Sato N(他4名)
  • Journal Title: Neurobiol Aging Volume: vol.34 Pages: 2064-2070
  • Peer Reviewed
• [Journal Article] 治療抵抗性高血圧とは、定義と頻度 (2013)
  • Author(s): 林真一郎、河野雄平
  • Journal Title: 血圧 Volume: 20巻 Pages: 517-523
  • URL: http://www.sentan.com/cgi-bin/db_n.cgi?mode=view_backno&no=985
• [Journal Article] 本態性高血圧患者を対象にしたアムロジピン5mg+イルベサルタン100mgの併用と、トリクロロメチアジド1mg+イルベサルタン100mgの併用に関する比較試験 (2013)
  • Author(s): 岩嶋義雄、林真一郎(他3名)
  • Journal Title: Therapeutic Research Volume: 34巻 Pages: 787-796
  • URL: http://www.lifescience.co.jp/tr/13/tr1306.html
• [Journal Article] 高血圧患者における降圧薬物の降圧度と腎機能および尿酸値の変化-GEANE研究サブスタデイー (2013)
  • Author(s): 大田祐子、林真一郎(他5名)
  • Journal Title: 日本未病システム学会雑誌 Volume: 19巻 Pages: 116-121
  • URL: http://www.mibyou.gr.jp/kikanshi.htm
• [Journal Article] コントロール不良高血圧患者を対象としたテルミサルタン/ヒドロクロロチアジド配合錠の降圧効果と代謝・腎機能への影響についての検討 (2013)
  • Author(s): 岩嶋義雄、林真一郎(他2名)
  • Journal Title: 血圧 Volume: 20巻 Pages: 517-523
  • URL: http://www.sentan.com/cgi-bin/db_n.cgi?mode=view_backno&no=954
• [Journal Article] Response to renal resistive index and cardiovascular and renal outcomes in essential hypertension (2013)
  • Author(s): Doi Y, Hayashi S 他
  • Journal Title: Hypertension Volume: 61
• [Journal Article] Control of home blood pressure with an amlodipine- or losarutan-based regimen and progression of carotid artery intima-media thickness in hypertensive patients: the HOSP sub study (2013)
  • Author(s): Ohta Y, Hayashi S 他
  • Journal Title: Clin Exp Hypertens Volume: 35 Pages: 279-284
  • Peer Reviewed
• [Journal Article] Effect of bezafibrate on office, home and ambulatory blood pressure in hypertensive patients with dyslipidemia (2013)
  • Author(s): Ohta Y, Hayashi S 他
  • Journal Title: J Hum Hypertens Volume: 60 Pages: 417-420
  • Peer Reviewed
• [Journal Article] 本態性高血圧患者を対象にしたアムロジピン5mg＋イルベサルタン100mgの併用と、トリクロルメチアジド1mg＋イルベサルタン100mgの併用に関する比較試験 (2013)
  • Author(s): 岩嶋義雄、林真一郎 他
  • Journal Title: Therapeutic Research Volume: 34 Pages: 787-796
• [Journal Article] 高血圧患者における降圧薬別の降圧度と腎機能および尿酸値の変化―GEANE研究サブスタデイー (2013)
  • Author(s): 大田祐子、林真一郎 他
  • Journal Title: 日本未病システム学会雑誌 Volume: 19 Pages: 116-121
• [Journal Article] コントロール不良高血圧患者を対象にしたテルミサルタン／ヒドロクロロチアジド配合錠の降圧効果と代謝・腎機能への影響についての検討 (2013)
  • Author(s): 岩嶋義雄、林真一郎 他
  • Journal Title: 血圧 Volume: 20 Pages: 517-523
• [Journal Article] Control of home blood pressure with an amlodipine- or losartan-based regimen and progression of carotid artery intima-media thickness in hypertensive patients: The HOSP Substudy (2013)
  • Author(s): Ohta Y, Hayashi S 他
  • Journal Title: Clin Exp Hypertens Volume: 未定
  • Peer Reviewed
• [Journal Article] Cilostazol regulates endothelial autophagy and preserves endothelial potential for re-endothelialization upon use of sirolimus-eluting stent (2013)
  • Author(s): Hayashi S
  • Journal Title: Japan Circulation Society News Volume: 未定
• [Journal Article] Guideline for the use and interpretation assays for monitoring autophagy (2012)
  • Author(s): Klionsky DJ, Hayashi S, Yamamoto A(他1267名、421名)
  • Journal Title: Autophagy Volume: vol.8 Pages: 445-544
  • URL: https://www.landesbioscience.com/journals/autophagy/article/19496/?nocache=1839736584
  • Peer Reviewed
• [Journal Article] Renal resistive index and cardiovascular and renal outcomes in essential hypertension (2012)
  • Author(s): Doi Y, Hayashi S 他
  • Journal Title: Hypertension Volume: 60 Issue: 3 Pages: 770
  • DOI: 10.1161/hypertensionaha.112.196717
  • Peer Reviewed
• [Journal Article] Human gastric cancer organize neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells (2012)
  • Author(s): Tawada M, Hayashi S(他3名)
  • Journal Title: vol.47 Pages: 1057-1060
  • NAID: 10031122093
  • Peer Reviewed
• [Journal Article] Differential regulation of amyloid precursor protein/presenilin 1 interaction during Ab40/42 production detected using fusion constructs (2012)
  • Author(s): Sato N
  • Journal Title: PLoS One Volume: 7 Issue: 11 Pages: e48551-e48551
  • DOI: 10.1371/journal.pone.0048551
  • Peer Reviewed
• [Journal Article] Human gastric cancer organize neighboring lymphatic vessels via recruitment of bone marrow-derived lymphatic endothelial progenitor cells (2012)
  • Author(s): Tawada M, Hayashi S 他
  • Journal Title: J Gastroenterol Volume: 47 Issue: 9 Pages: 1057-1060
  • DOI: 10.1007/s00535-012-0638-4
  • NAID: 10031122093
  • Peer Reviewed
• [Journal Article] Guidelines for the use and interpretation of assays for monitoring autophagy (2012)
  • Author(s): Klionsky DJ, Hayashi S 他
  • Journal Title: Autophagy Volume: 8 Pages: 1-100
  • Peer Reviewed
• [Presentation] Cyclic strain and oxidative stress mediated smad6 regulation correlates with vascular endothelial autophagy and dysfunction (2014)
  • Author(s): Hayashi S
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2014-03-21
• [Presentation] Renal dopler sonography predicts cardiovascular and renal outcomes (2014)
  • Author(s): Kusunoki H, Hayashi S 他
  • Organizer: The 18th International Vascular Biology Meeting
  • Place of Presentation: Kyoto, Japan
• [Presentation] Cyclic Strain and Oxidative Stress Mediated Smad6 Regulation Correlates with Vascular Endothelial Autophagy and Dysfunction (2014)
  • Author(s): Hayashi S
  • Organizer: 第78回日本循環器学会学術集会
  • Place of Presentation: 東京
• [Presentation] 高血圧におけるオートファジー制御 (2013)
  • Author(s): 林真一郎
  • Organizer: 日本高血圧学会
  • Place of Presentation: 大阪
  • Year and Date: 2013-10-25
• [Presentation] 高血圧発症早期における血管内皮細胞の微小構造変化 (2013)
  • Author(s): 林真一郎
  • Organizer: 臨床高血圧フォーラム
  • Place of Presentation: 東京
  • Year and Date: 2013-05-26
• [Presentation] Cilostazol regulates endothelial autophagy and preserves endothelial potential for re-endothelialization upon use of sirolimus-eluting-stent (2013)
  • Author(s): Hayashi S
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2013-03-16
• [Presentation] Phenotypic alterations of brain microvascular endothelium in a murine model of Alzheimer disease (2013)
  • Author(s): Hayashi S
  • Organizer: International Stroke Conference
  • Place of Presentation: Honolulu、USA
  • Year and Date: 2013-02-08
• [Presentation] Oxidative stress and cyclic strain mediated smad6 regulation in vascular endothelial cells correlates with autophagy induction and endothelial dysfunction (2013)
  • Author(s): Hayashi S
  • Organizer: International Stroke Conference
  • Place of Presentation: Honolulu、USA
  • Year and Date: 2013-02-06
• [Presentation] 高血圧における血管内皮のオートファジー制御 (2013)
  • Author(s): 林真一郎
  • Organizer: 第36回日本高血圧学会
  • Place of Presentation: 大阪
• [Presentation] 高血圧患者における夜間尿と塩分摂取量簡易測定器による食塩摂取量自己測定の実用性と減塩への効果 (2013)
  • Author(s): 河野雄平、林真一郎 他
  • Organizer: 第36回日本高血圧学会
  • Place of Presentation: 大阪
• [Presentation] 高血圧発症早期における血管内皮細胞の微小構造変化 (2013)
  • Author(s): 林真一郎 他
  • Organizer: 第2回臨床高血圧フォーラム
  • Place of Presentation: 東京
• [Presentation] Phenotypic alterations of brain microvascular endothelium in a murine model of Alzheimer disease (2013)
  • Author(s): Hayashi S
  • Organizer: International Stroke Conference
  • Place of Presentation: Honolulu, USA
• [Presentation] Oxidative stress and cyclic strain mediated smad6 regulation in vascular endothelial cells correlates with autophagy induction and endothelial dysfunction (2013)
  • Author(s): Hayashi S
  • Organizer: International Stroke Conference
  • Place of Presentation: Honolulu, USA
• [Presentation] Cilostazol regulates endothelial autophagy and preserves endothelial potential for re-endothelialization upon use of sirolimus-elutingsten (2013)
  • Author(s): Hayashi S
  • Organizer: 第77回日本循環器学会学術集会
  • Place of Presentation: みなとみらい、横浜
• [Presentation] Endothelial autophagy and dysfunction are triggered by a cyclic strain mediated Smad6 regulation (2012)
  • Author(s): Hayashi S
  • Organizer: International Symposium on Autophagy
  • Place of Presentation: 沖縄
  • Year and Date: 2012-10-29
• [Presentation] Phosphodiesterae III inhibitor reduces vascular endothelial autophagy leading to an enhancement of re-endothelialization under the use of sirolimus (2012)
  • Author(s): Hayashi S
  • Organizer: Meeting of International Society of Hypertension
  • Place of Presentation: Sydney、Australia
  • Year and Date: 2012-10-03
• [Presentation] Autophagy cascades correlates with phenotypic alteration of neurovascular endothelium in a mouse model of Alzheimer disease (2012)
  • Author(s): Hayashi S
  • Organizer: Meeting of International Society of Hypertension
  • Place of Presentation: Sydney、Australia
  • Year and Date: 2012-10-02
• [Presentation] Phenotypic alteration of neurovascular endothelium in a mouse model of Alzheimer disease (2012)
  • Author(s): 林真一郎
  • Organizer: 日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2012-03-18
• [Presentation] Autophagy Cascade Correlates With Phenotypic Alteration of Neurovascular Endothelium in a Mouse Model Of Alzheimer Disease (2012)
  • Author(s): Hayashi S
  • Organizer: 24th Meeting of the International Society of Hypertension
  • Place of Presentation: Sydney, Australia
• [Presentation] PhosphodiesteraseIII Inhibitor Reduces Vascular Endothelial Autophagy Leading To an Enhancement of Re-Endothelialization under the Use of Sirolimus (2012)
  • Author(s): Hayashi S
  • Organizer: 24th Meeting of the International Society of Hypertension
  • Place of Presentation: Sydney, Australia
• [Presentation] Endothelial autophagy and dysfunction are triggered by a cyclic strain mediated Smad6 regulation (2012)
  • Author(s): Hayashi S
  • Organizer: The 6th International Symposium on Autophagy
  • Place of Presentation: Okinawa, Japan
• [Presentation] Phenotypic alteration of neurovascular endothelium in a mouse model of Alzheimer disease
  • Author(s): 林真一郎
  • Organizer: 第76回日本循環器病学会学術集会
  • Place of Presentation: 福岡国際会議場
• [Book] 血管再生治療-現状から未来を展望する (2012)
  • Author(s): 林真一郎他
  • Total Pages: 264
  • Publisher: 診断と治療社
• [Book] 血管再生治療ー現状から未来を展望する。 (2012)
  • Author(s): 林真一郎（分担執筆）
  • Total Pages: 264
  • Publisher: 診断と治療社