Role of oxidised HDL in the pathogenesis of coronary artery atherosclerosis

• Project/Area Number: 18K08049
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Juntendo University
• Principal Investigator: Hiroshi Iwata 順天堂大学, 医学部, 准教授 (00451807)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: HDL機能 / ApoA1 / 動脈硬化 / 悪性腫瘍 / 予後 / 心房細動 / バイオマーカー / プロテオミクス / 酸化HDL / コレステロール引き抜き能

Outline of Final Research Achievements

Despite an established prognostic significance of low high-density cholesterol (HDL)　level in the context of atherosclerotic cardiovascular disease, recent failure of clinical trials of HDL raising drugs have caused less enthusiasm regarding its clinical and mechanistic exploration. However, since the functionality of HDL has been suggested to be significant, we addressed that in patients with coronary artery disease for prediction of all-cause and cancer mortalities. In addition, the significance of HDL functionality was evaluated in the pathology of atrial fibrillation (AF). As consequences, level of ApoA1, the main component of HDL particle, was a more sensitive marker to predict all-cause and cancer mortalities than HDL. Moreover, reduced HDL functionality, represented by cholesterol efflux capacity (CEC) was associated with enlarged left atrium volume index (LAVI) in AF patients, indicating any anti-remodeling role of HDL in the pathogenesis of AF.

Academic Significance and Societal Importance of the Research Achievements

HDLは、その低値が動脈硬化リスクであることがエビデンスとして確立されているものの、LDL(low density lipoprotein)や中性脂肪に比べ、冠動脈疾患や脳血管疾患など動脈硬化性疾患の治療標的としての地位は高くない。本研究ではそのHDLの、動脈硬化性疾患・不整脈更には悪性腫瘍における役割とその可能性について様々な検討を行なった。その結果、HDLの量(血中HDL濃度)のみでは測れないHDL機能(コレステロール引き抜き能)などに多面的な役割が示され、治療標的としても、動脈硬化だけでなく不整脈や悪性腫瘍にも応用できる可能性が示された。

Research Products

• [Journal Article] Cite Share Predictors of discordance between fractional flow reserve and resting full-cycle ratio in patients with coronary artery disease: Evidence from clinical practice. (2021)
  • Author(s): Kato Y, Dohi T, Chikata Y, Fukase T, Takeuchi M, Takahashi N, Endo H, Nishiyama H, Doi S, Okai I, Iwata H, Isoda K, Okazaki S, Miyauchi K, Daida H, Minamino T.
  • Journal Title: J Cardiol. Volume: 77 Issue: 3 Pages: 313-9
  • DOI: 10.1016/j.jjcc.2020.10.014
  • Peer Reviewed
• [Journal Article] The association between impairment of HDL cholesterol efflux capacity and atrial remodeling in atrial fibrillation (2021)
  • Author(s): Minami-Takano A, Iwata H, Miyosawa K, Shiozawa T, Hayashi H, Funamizu T, Ishii K, Nozaki Y, Tabuchi H, Sekita G, Shimada K, Sumiyoshi M, Nakazato Y, Daida H, Minamino T.
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 3547-3547
  • DOI: 10.1038/s41598-021-82998-4
  • Peer Reviewed / Open Access
• [Journal Article] Enhanced monocyte migratory activity in the pathogenesis of structural remodeling in atrial fibrillation (2020)
  • Author(s): Katsutoshi Miyosawa, Hiroshi Iwata, Asuka Minami-Takano, Hidemori Hayashi, Haruna Tabuchi, Gaku Sekita, Tomoyasu Kadoguchi, Kai Ishii, Yui Nozaki, Takehiro Funamizu, Yuichi Chikata, Satoshi Matsushita, Atsushi Amano, Masataka Sumiyoshi, Yuji Nakazato, Hiroyuki Daida, Tohru Minamino
  • Journal Title: PLoS ONE Volume: 15 Issue: 10 Pages: 1-16
  • DOI: 10.1371/journal.pone.0240540
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous Estimation of Gender Male and Atrial Fibrillation as Risk Factors for Adverse Outcomes Following Transcatheter Aortic Valve Implantation. (2020)
  • Author(s): Chikata Y, Iwata H, Doi S, Funamizu T, Okazaki S, Dohi S, Higuchi R, Saji M, Takamisawa I, Tamura H, Amano A, Daida H, Minamino T.
  • Journal Title: J Clin Med. Volume: 7 Issue: 12 Pages: 3963-3963
  • DOI: 10.3390/jcm9123963
  • Peer Reviewed / Open Access
• [Journal Article] Novel Nutritional Index Serves as A Useful Prognostic Indicator in Cardiac Critical Patients Requiring Mechanical Circulatory Support. (2019)
  • Author(s): Minami-Takano A, Iwata H, Miyosawa K, Kubota K, Kimura A, Osawa S, Shitara M, Okazaki S, Suwa S, Miyauchi K, Sumiyoshi M, Amano A, Daida H
  • Journal Title: Nutrients Volume: 24 Issue: 6 Pages: 1420-1420
  • DOI: 10.3390/nu11061420
  • Peer Reviewed / Open Access
• [Presentation] Statins Were Effective to Lower Long-Term Cardiovascular Mortalities in Patients Treated by Chronic Hemodialysis Underwent Percutaneous Coronary Intervention (2019)
  • Author(s): Funamizu T, Iwata H, Chikata Y, Doi S, Endo H, Wada H, Naito R, Konishi H, Ogita M, Kato Y, Okai I, Dohi T, Kasai T, Isoda K, Okazaki S, Miyauchi K
  • Organizer: American Heart Association
  • Int'l Joint Research