Disease susceptibility gene analysis of patients with coronary vasospasm

• Project/Area Number: 17K09491
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: University of Yamanashi
• Principal Investigator: NAKAMURA Takamitsu 山梨大学, 大学院総合研究部, 助教 (60377512)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2019: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 冠攣縮性狭心症 / 中膜 / 内膜 / 遺伝子 / 脂質異常症 / 画像診断

Outline of Final Research Achievements

Of 164 patients with coronary artery spasm, family history of coronary artery disease was observed in 19 (11.9%) patients. Patients with family history had higher levels of ApoCIII/CII ratio, suggesting genetic factors related to dyslipidemia may contribute to susceptibility of coronary spasm, Moreover, the optical coherence tomography(OCT) and the vasomotor response to ACh were assessed in patients with previous myocardial infarction. The coronary contractile response to ACh had a positive linear relationship with medial area. The contractile response increased as the intimal layer thickened up to the inflection point; thereafter, the contractile response declined. However, there were no significant differences in risk factors and genes variable between patients with and without increased.

Academic Significance and Societal Importance of the Research Achievements

冠動脈の攣縮は、冠攣縮性狭心症のみならず種々の虚血性心疾患の病態悪化に影響を及ぼすことが知られている。しかしながら、冠攣縮を引き起こす原因については未だはっきりしていないところが多い。本研究では、冠攣縮の家族歴を有する症例では、他の冠動脈疾患のような動脈硬化危険因子は認めなかった。また、光干渉断層像(OCT)を用いた評価では、冠攣縮の病態悪化に冠動脈血管の中膜の増大が関与している可能性が示唆された。中膜増大に関与する臨床因子や遺伝因子については明らかな差は認めなかった。

Research Products

• [Journal Article] Improvement of Endothelial Dysfunction Is Mediated Through Reduction of Remnant Lipoprotein After Statin Therapy in Patients With Coronary Artery Disease (2020)
  • Author(s): Nakamura T, Uematsu M, Yoshizaki T, Kobayashi T, Watanabe Y, Kugiyama K.
  • Journal Title: J Cardiol. Volume: 75 Issue: 3 Pages: 270-274
  • DOI: 10.1016/j.jjcc.2019.08.006
  • Peer Reviewed / Open Access
• [Journal Article] Relationship of a Thinned Medial Layer to the Attenuated Contractile Response in Atherosclerotic Coronary Arteries (2020)
  • Author(s): Nakamura T, Horikoshi T, Kugiyama K.
  • Journal Title: Am J Physiol Heart Circ Physiol . Volume: 318 Issue: 1 Pages: H135-H142
  • DOI: 10.1152/ajpheart.00537.2019
  • Peer Reviewed
• [Journal Article] Persistent Dysfunction of Coronary Endothelial Vasomotor Responses is Related to Atheroma Plaque Progression in the Infarct-Related Coronary Artery of AMI Survivors (2019)
  • Author(s): Horikoshi T, Obata JE, Nakamura T, Fujioka D, Watanabe Y, Nakamura K, Watanabe K, Saito Y, Kugiyama K.
  • Journal Title: Journal of Atherosclerosis and Thrombosis Volume: 26 Issue: 12 Pages: 1062-1074
  • DOI: 10.5551/jat.48249
  • NAID: 130007754400
  • ISSN: 1340-3478, 1880-3873
  • Year and Date: 2019-12-01
  • Peer Reviewed / Open Access
• [Journal Article] Remnant Lipoproteins Are Residual Risk Factor for Future Cardiovascular Events in Patients With Stable Coronary Artery Disease and On-Statin Low-Density Lipoprotein Cholesterol Levels <70 mg/dL (2019)
  • Author(s): Fujihara Y, Nakamura T, Horikoshi T, Obata JE, Fujioka D, Watanabe Y, Watanabe K, Kugiyama K.
  • Journal Title: Circulation Journal Volume: 83 Issue: 6 Pages: 1302-1308
  • DOI: 10.1253/circj.CJ-19-0047
  • NAID: 130007652779
  • ISSN: 1346-9843, 1347-4820
  • Year and Date: 2019-05-24
  • Peer Reviewed / Open Access
• [Journal Article] Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction. (2019)
  • Author(s): Nakamura T, Uematsu M, Deyama J, Watanabe Y, Nakamura K, Kobayashi T, Saito Y, Fujioka D, Kawabata KI, Obata JE, Kugiyama K.
  • Journal Title: J Card Fail. Volume: Epub ahead of print Issue: 9 Pages: 725-732
  • DOI: 10.1016/j.cardfail.2019.02.019
  • Peer Reviewed / Open Access
• [Journal Article] High levels of stromal cell-derived factor-1α predict short-term progression of renal dysfunction in patients with coronary artery disease. (2019)
  • Author(s): Uematsu M, Nakamura T, Yoshizaki T, Watanabe Y, Deyama J, Watanabe K, Kobayashi T, Fujioka D, Saito Y, Nakamura K, Kawabata K, Obata JE, Kugiyama K.
  • Journal Title: Clin Exp Nephrol. Volume: Epub ahead of print Issue: 7 Pages: 920-927
  • DOI: 10.1007/s10157-019-01722-9
  • Peer Reviewed
• [Journal Article] Effect of coronary artery spasm on long-term outcomes in survivors of acute myocardial infarction. (2018)
  • Author(s): Deyama J, Nakamura T, Saito Y, Obata JE, Fujioka D, Nakamura K, Watanabe K, Kugiyama K.
  • Journal Title: Int J Cardiol. Volume: 257 Pages: 7-11
  • DOI: 10.1016/j.ijcard.2017.08.002
  • Peer Reviewed
• [Presentation] Pulmonary Vascular Resistance Is Associated With Brachial-Ankle Pulse-Wave Velocity and Adverse Clinical Outcomes in Patients With Heart Failure With Preserved Ejection Fraction. (2018)
  • Author(s): Nakamura T, Uematsu M, Deyama J, Watanabe Y, Nakamura K, Kobayashi T, Saito Y, Fujioka D, Kawabata KI, Obata JE, Kugiyama K.
  • Organizer: American Heart Association Scientific Session 2018
  • Int'l Joint Research
• [Remarks] 山梨大学第2内科ホームページ
  • URL: https://yamanashi-2nai.com
• [Remarks] 山梨大学第２内科ホームページ
  • URL: http://yamanashi-2nai.com