Hypoxic stress in sleep apnea causes systemic inflammation and promotes atherosclerosis.

• Project/Area Number: 19390226
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Nara Medical University
• Principal Investigator: KIMURA Hiroshi Nara Medical University, 医学部, 教授 (20195374)
• Co-Investigator(Kenkyū-buntansha): TAMAKI Shinji 奈良県立医科大学, 医学部, 助教 (30347546) ; YAMAUCHI Motoo 奈良県立医科大学, 医学部, 助教 (30405378) ; TOMODA Koichi 奈良県立医科大学, 医学部, 講師 (90364059) ; YOSHIKAWA Masanori 奈良県立医科大学, 医学部, 准教授 (80271203) ; HAMADA Kaoru 奈良県立医科大学, 医学部, 教授 (80228535) ; MAKINODAN Kiyoshi 奈良県立医科大学, 医学部, 医員 (50382304)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000); Fiscal Year 2009: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2008: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2007: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 睡眠時無呼吸 / 低酸素ストレス / 動脈硬化 / 単球 / 炎症性サイトカイン / アディポサイトカイン / 間歇的低酸素 / 内臓脂肪細胞 / メタボリックシンドローム / 血管内皮細胞 / アディポネクチン / 内臓脂肪 / 酸化ストレス

Research Abstract

Obstructive sleep apnea syndrome (OSAS) is frequently associated with the complication of the cardiovascular diseases. However, the precise mechanism causing atherosclerosis has not been fully elucidated. We demonstrated that the productions of inflammatory mediators such as TNF-α and MCP-1 by monocytes were significantly elevated in OSAS patients as compared to in the control subjects. The invasive ability of monocytes evaluated by Matrigel Invasion Chamber was also significantly elevated in OSAS compared to in the control. Furthermore, we demonstrated the experimental exposure to intermittent hypoxia caused not only the increase in the production of inflammatory cytokines by monocytes, but also the decrease in the secretion of adipocytokines by visceral adipocytes of rats.

Research Products

• [Journal Article] Production of inflammatory mediators by monocytes in patients with obstructive sleep apnea syndrome. (2009)
  • Author(s): Tamaki S, Yamauchi M, Fukuoka A, Makinodan K, Koyama N, Tomoda K, Yoshikawa Li, Kimura H.
  • Journal Title: Internal Medicine. 48 Pages: 1255-1262
  • NAID: 130000121950
  • Peer Reviewed
• [Journal Article] Nocturnal hypoxic stress activates invasive ability of monocytes in patients with obstructive sleep apnoea syndrome. (2009)
  • Author(s): Tamaki S, Yamauchi M, Fukuoka A, Makinodan K, Koyama N, Tomoda K, Yoshikawa M, Kimura H.
  • Journal Title: Respirology 14 Pages: 689-694
  • Peer Reviewed
• [Journal Article] Simple four-variable screening tool for identification of patients with sleep-disordered breathing. (2009)
  • Author(s): Takegami M, Hayashino Y, Chin K, Sokejima S, Kadotani H, Akashiba T, Kimura Ohi M, Fukuhara S.
  • Journal Title: Sleep. 32 Pages: 939-948
  • Peer Reviewed
• [Journal Article] 内分泌疾患と睡眠呼吸障害. (2009)
  • Author(s): 山内基雄, 木村弘.
  • Journal Title: Modern Pkysician 29 Pages: 1149-1151
• [Journal Article] 睡眠時無呼吸の薬物療法と新薬の展開 (2009)
  • Author(s): 山内基雄, 木村弘
  • Journal Title: 最新医学 64 Pages: 89-93
• [Journal Article] Production of inflammatory mediators by monocytes in patients with obstructive sleep apnea syndrome (2009)
  • Author(s): Tamaki S, Kimura H, et al.
  • Journal Title: Internal Medicine 48 Pages: 1255-1262
  • NAID: 130000121950
  • Peer Reviewed
• [Journal Article] Nocturnal hypoxic stress activates invasive ability of monocytes in patients with obstructive sleep apnoea syndrome (2009)
  • Author(s): Tamaki S, Kimura H, et al.
  • Journal Title: Respirology 14 Pages: 689-694
  • Peer Reviewed
• [Journal Article] Simple four-variable screening tool for identification of patients with sleep- disordered breathing (2009)
  • Author(s): Takegami M, Kimura H, et al.
  • Journal Title: Sleep 32 Pages: 939-948
  • Peer Reviewed
• [Journal Article] 内分泌疾患と睡眠呼吸障害 (2009)
  • Author(s): 山内基雄, 木村弘
  • Journal Title: Modern Physician 29 Pages: 1149-1151
• [Journal Article] (2009)
  • Author(s): 玉置伸二, 木村弘
  • Journal Title: 睡眠時無呼吸症候群-SASと全身性炎症(克誠堂出版) Pages: 82-87
• [Journal Article] Oxidative stress in obstructive sleep apnea: putative pathways to the cardiovascular complications. (2008)
  • Author(s): Yamauchi M, Kimura H.
  • Journal Title: Antioxid Redox Signal. 10 Pages: 755-768
  • Peer Reviewed
• [Journal Article] Effect of serum leptin levels on hypercapnic ventilatory response in obstructive sleep apnea. (2008)
  • Author(s): Makinodan K, Yoshikawa hi, Fukuoka A, Tamaki S, Koyama N, Yamauchi H, Tomoda K, Hamada K, Kimura H.
  • Journal Title: Respiration. 75 Pages: 257-364
• [Journal Article] Oxidative stress in obstructive sleep apnea : putative pathways to the cardiovascular complications. (2008)
  • Author(s): Yamauchi M, Kimura H.
  • Journal Title: Antioxid Redox Signal. 10 Pages: 755-768
  • Peer Reviewed
• [Journal Article] Oxidative stress in obstructive sleep apnea: putative pathways to the cardiovascular complications (2008)
  • Author(s): Yamauchi M and Kimura H
  • Journal Title: Antioxidants & Redox signaling 10 Pages: 755-768
• [Presentation] Intermittent hypoxia-specific express of CCL2, CXCL9, and CXCL10 genes via NFkapppaB activation in pancreatic beta cells. (2009)
  • Author(s): Ota H, Kimura H, et al.
  • Organizer: 45th Annual meeting of European Association for the Study of Diabetes.
  • Place of Presentation: Vienna, Austria.
  • Year and Date: 2009-09-30
• [Presentation] Should mixed apnoea be classified with obstructive apnea? (2009)
  • Author(s): Yamauchi M, Kimura H, et al.
  • Organizer: European Respiratory Society Annual Congress.
  • Place of Presentation: Vienna, Austria.
  • Year and Date: 2009-09-15
• [Presentation] Should mixed apnoea be classified with obstructive apnea? (2009)
  • Author(s): 山内基雄, 木村弘, et al.
  • Organizer: European Respiratory Society Annual Congress
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2009-09-15
• [Presentation] Should mixed apnoea be classified with obstruc tive apnea? (2009)
  • Author(s): Yamauchi M, Kimura H, et al.
  • Organizer: The 11th International Symp osium on Sleep & Breathing.
  • Place of Presentation: Pittsburg, USA.
  • Year and Date: 2009-09-12
• [Presentation] Should mixed apnoea be classified with obstructive apnea? (2009)
  • Author(s): 山内基雄, 木村弘, et al.
  • Organizer: The 11^<th> International Symposium on Sleep & Breathing
  • Place of Presentation: Pittsburg, USA
  • Year and Date: 2009-09-12
• [Presentation] 臍帯静脈血管内皮細胞における間歇的低酸素曝露によるvon Willebrand factorの変化の検討. (2009)
  • Author(s): 児山紀子, 木村弘, 他7名
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-14
• [Presentation] 臍帯静脈血管内皮細胞における間歇的低酸素曝露による von Willebrand factor の変化の検討 (2009)
  • Author(s): 児山紀子, 木村弘, 他7名
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-14
• [Presentation] 閉塞型睡眠時無呼吸症候群/肥満低換気症候群におけるメタボリックシンドローム合併症例の検討. (2009)
  • Author(s): 玉置伸二, 木村弘, 他8名
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13
• [Presentation] Spontaneous apneaとPost-sigh apneaに対するセロトニン1A受容体アゴニストの効果. (2009)
  • Author(s): 山内基雄, Strohl Kingman, 木村弘
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13
• [Presentation] 閉塞型睡眠時無呼吸症候群/肥満低換気症候群におけるメタボリックシンドローム合併症例の検討 (2009)
  • Author(s): 玉置伸二, 木村弘, 他8名
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13
• [Presentation] Spontaneous apnea と Post-sigh apnea に対するセロトニン1A受容体アゴニストの効果 (2009)
  • Author(s): 山内基雄, Strohl Kingman, 木村弘
  • Organizer: 第49回日本呼吸器学会学術講演会
  • Place of Presentation: 東京
  • Year and Date: 2009-06-13
• [Presentation] Intermittent hypoxia-specific express of CCL2, CXCL9, and CXCL10 genes via NFkapppaB activation in pancreatic beta cells (2009)
  • Author(s): Ota H, Kimura H, et al.
  • Organizer: 45th Annual meeting of European Association for the Study of Diabetes
  • Place of Presentation: Vienna, Austria
• [Presentation] 間歇的低酸素曝露が内臓脂肪細胞からのアディポサイトカイン産生能に及ぼす影響 (2008)
  • Author(s): 玉置使二, 木村弘, 他7名
  • Organizer: 第48回日本呼吸器学会学術講演会
  • Place of Presentation: 神戸
  • Year and Date: 2008-06-15
• [Presentation] Sleep disordered breathing and hypoxic adaptation. (2008)
  • Author(s): Kimura H.
  • Organizer: (Scientific sy mposium) American Thoracic Society 2008.
  • Place of Presentation: Toronto, Canada.
  • Year and Date: 2008-05-18
• [Presentation] Intermitten t hypoxia activates production of inflammatory cytokines by monocytes. (2008)
  • Author(s): Tamaki S, Kimura H, et al.
  • Organizer: Thoracic Society 2008.
  • Place of Presentation: Toronto, Canada.
  • Year and Date: 2008-05-18
• [Presentation] Sleep disordered breathing and hypoxic adaptation (2008)
  • Author(s): 木村 弘
  • Organizer: American Thoracic Society (ATS) 2008
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-05-18
• [Presentation] Intermittent hypoxia activates production of inflammatory cytokines by monocytes (2008)
  • Author(s): 玉置伸二, 木村 弘, 他7名
  • Organizer: American Thoracic Society (ATS) 2008
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2008-05-18
• [Presentation] OSAにおける低酸素ストレスと動脈硬化病変 (2007)
  • Author(s): 玉置伸二, 本村弘, 他6名
  • Organizer: 日本睡眠学会第32回定期学術集会シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-05-12
• [Presentation] 間歇的低酸素暴露がヒト単球細胞からのサイトカイン産生能に及ぼす影響. (2007)
  • Author(s): 玉置伸二, 木村弘, 他7名
  • Organizer: 第47回日本呼吸器学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-12
• [Presentation] 間欺的低酸素暴露がヒト単球細胞からのサイトカイン産生能に及ぼす影響 (2007)
  • Author(s): 玉置 伸二、木村 弘, 他7名
  • Organizer: 第47回日本呼吸器学会総会
  • Place of Presentation: 東京
  • Year and Date: 2007-05-12
• [Book] 睡眠時無呼吸症候群-SASと全身性炎症 (2009)
  • Author(s): 玉置伸二, 木村弘
  • Publisher: 克誠堂出版