Investigation of the pathogenesis and progression of cardiovascular diseases in patients with obstructive sleep apnea

• Project/Area Number: 26860217
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Nara Medical University
• Principal Investigator: Kyotani Yoji 奈良県立医科大学, 医学部, 助教 (10706534)
• Research Collaborator: TAKASAWA Shin
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Obstructive sleep apnea / vascular smooth muscle / epiregulin / interleukin-6 / インターロイキン-6 / 間歇的低酸素 / 睡眠時無呼吸症候群 / 間歇的低酸素症 / 血管平滑筋細胞

Outline of Final Research Achievements

Sleep apnea (SA) is characterized by intermittent hypoxia (IH) and a risk factor for atherosclerosis which consequently cause myocardial infarction (MI). We finally aim to discover the prophylaxis against MI and previously found out that IH induced a increase of epiregulin which had a relation to atherosclerosis. However, its underlying mechanisms have been remained. In this study, we show that the proinflammatory cytokine IL-6 might be involved in the IH-induced increase of epiregulin. IL-6 has a relation to several inflammatory diseases and may play a pivotal role in the progression of MI and inflammatory diseases including autoimmune disease in patients with SA. IL-6 and its increase in IH may be an important for the establish of prophylaxis.

Research Products

• [Journal Article] Exendin-4 Prevents Vascular Smooth Muscle Cell Proliferation and Migration by Angiotensin II via the Inhibition of ERK1/2 and JNK Signaling Pathways (2015)
  • Author(s): Kosuke Nagayama, Yoji Kyotani, Jing Zhao, Satoyasu Ito, Kentaro Ozawa, Francesco A. Bolstad, Masanori Yoshizumi
  • Journal Title: Plos One Volume: 10 Issue: 9 Pages: e0137960-e0137960
  • DOI: 10.1371/journal.pone.0137960
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Olmesartan inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch through the inhibition of the c-Jun N-terminal kinase and p38 signaling pathways (2015)
  • Author(s): Satoyasu Ito, Kentaro Ozawa, Jing Zhao, Yoji Kyotani, Kosuke Nagayama, Masanori Yoshizumi
  • Journal Title: Journal of Pharmacological Sciences Volume: 127 Issue: 1 Pages: 69-74
  • DOI: 10.1016/j.jphs.2014.11.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Azelnidipine inhibits cultured rat vascular smooth muscle cell death induced by cyclic mechanical stretch (2014)
  • Author(s): Jing Zhao, Kentaro Ozawa, Yoji Kyotani, Kosuke Nagayama, Satoyasu Ito, Akira T Komatsubara, Yuichi Tsuji, Masanori Yoshizumi
  • Journal Title: PloS One Volume: 9 Issue: 7 Pages: e102813-e102813
  • DOI: 10.1371/journal.pone.0102813
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 周期性の低酸素負荷または伸展負荷に対する血管平滑筋細胞応答と動脈硬化 (2016)
  • Author(s): 京谷 陽司、高沢 伸、趙 昌、小澤 健太郎、吉栖 正典
  • Organizer: 第89回 日本薬理学会年会
  • Place of Presentation: パシフィコ横浜 会議センター
  • Year and Date: 2016-03-09
• [Presentation] Sleep apnea syndrome as an emerging risk factor for type 2 diabetes and atherosclerosis: evidence and underlying mechanism (2014)
  • Author(s): Yoji Kyotani, Hiroyo Ota, Asako Itaya-Hironaka, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Jing Zhao, Kosuke Nagayama, Kentaro Ozawa, Shin Takasawa, Hiroshi Kimura, Masanori Yoshizumi
  • Organizer: 9th Metabolic Syndrome, Type 2 Diabetes and Atherosclerosis Congress
  • Place of Presentation: Kyoto International Conference Center
  • Year and Date: 2014-09-12 – 2014-09-14