Inhibitors of vascular calcification in the development and prognosis of polyvascular disease

• Project/Area Number: 19K17589
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Shinshu University
• Principal Investigator: Senda Keisuke 信州大学, 医学部附属病院, 特任研究員 (00794413)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2021: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2020: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
• Keywords: 動脈硬化 / 血管石灰化 / 石灰化抑制因子 / 全身性動脈硬化疾患 / FGF-23 / Osteoprotegerin / Fetuin-A / 動脈硬化疾患 / 冠動脈石灰化 / 大動脈石灰化 / 大動脈弁石灰化 / 全身動脈硬化疾患 / 検体採取終了 / Baseline評価中 / 学会演題登録中 / 検体採取開始

Outline of Research at the Start

本邦では超高齢化社会の進行と共に動脈硬化性疾患患者が増加している。動脈硬化の一つの形態として血管石灰化が挙げられる。血管石灰化は、以前から動脈硬化の末期と理解されてきたが、最近の研究により石灰化抑制機構の異常が報告され、血管石灰化が進行する患者の血清では、血中の石灰化抑制因子が低下していると言われている。通常は動脈硬化は全身に及ぶため、冠動脈疾患、脳動脈疾患、下肢動脈疾患などを併発している患者が多い。一方で、しばしば特定の血管にのみ石灰化がみられる症例もみられるが、その理由は定かではない。本研究では、石灰化抑制因子の濃度と全身血管石灰化の程度を検討し、その後の心血管イベントとの関連を検証する。

Outline of Final Research Achievements

We investigated the association of Fibroblast growth factor 23 (FGF-23), Osteoprotegerin (OPG), and Fetuin-A with polyvascular disease. FGF-23 was significantly correlated with coronary artery calcification and aortic calcification in particular, while OPG was a possible marker for early atherosclerosis. In addition, semiquantitative analysis of abdominal aortic calcification by radiographs could noninvasively predict coronary artery calcification, suggesting that it may be useful as a screening test for cardiovascular disease. Aortic valve calcification was not associated with vascular calcification or the above-mentioned calcification inhibitory factors, suggesting a different calcification mechanism.

Academic Significance and Societal Importance of the Research Achievements

本研究では、石灰化抑制因子の血中濃度と全身の動脈の石灰化の関連を調査するため、冠動脈疾患患者の全身の血管スクリーニングを行い、相関があるかどうかを検証した。結果、FGF-23が動脈硬化疾患存在の優れた予測因子であることがわかった。今後さらに経過を追い心血管イベントと関連するかを検証すれば、予後予測も可能となり得る。その場合、予防的な抗血小板薬やスタチン製剤の使用、PやCaの管理などの積極的介入の意義につき、科学的基盤が確立できる。

Research Products

• [Journal Article] The Impact of Hyperuricemia on Patients With Low Body Mass Index After Endovascular Treatments: Data From the I-PAD Registry (2022)
  • Author(s): Nagae Ayumu、Ebisawa Soichiro、Saigusa Tatsuya、Nishikawa Ken、Fujimori Koki、Yui Hisanori、Maruyama Shusaku、Nakamura Chie、Kashiwagi Daisuke、Kobayashi Hideki、Sakai Takahiro、Senda Keisuke、Kato Tamon、Miura Takashi、Okada Ayako、Motoki Hirohiko、Kuwahara Koichiro
  • Journal Title: Angiology Volume: Online ahead of print Issue: 8 Pages: 753-763
  • DOI: 10.1177/00033197211072344
  • Peer Reviewed
• [Journal Article] Association of the Prognosis of Ankle-brachial Index Improvement One Year Following Endovascular Therapy in Patients with Peripheral Artery Disease: Data from the I-PAD NAGANO Registry (2021)
  • Author(s): Senda Keisuke、Miura Takashi、Kato Tamon、Kanzaki Yusuke、Abe Naoyuki、Yokota Daisuke、Yanagisawa Takashi、Okina Yoshiteru、Wakabayashi Tadamasa、Oyama Yushi、Karube Kenichi、Itagaki Tadashi、Yoda Hidetsugu、Shoin Kyoko、Oguchi Yasutaka、Aizawa Katsuyuki、Suzuki Chihiro、Kuwahara Koichiro
  • Journal Title: Internal Medicine Volume: 60 Issue: 13 Pages: 1999-2006
  • DOI: 10.2169/internalmedicine.6117-20
  • NAID: 130008060446
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-07-01
  • Peer Reviewed / Open Access
• [Journal Article] An Infected Popliteal Aneurysm after Plain Old Balloon Angioplasty (2021)
  • Author(s): Senda Keisuke、Yoda Hidetsugu、Shoin Kyoko、Oguchi Yasutaka、Aizawa Katsuyuki、Aso Shinichi、Shirai Erio、Kikuchi Niro、Ohtsu Yoshinori、Tsunemoto Hideo、Suzuki Chihiro
  • Journal Title: Internal Medicine Volume: 60 Issue: 1 Pages: 73-77
  • DOI: 10.2169/internalmedicine.5250-20
  • NAID: 130007965452
  • ISSN: 0918-2918, 1349-7235
  • Year and Date: 2021-01-01
  • Peer Reviewed / Open Access
• [Journal Article] Body composition and mortality in patients undergoing endovascular treatment for peripheral artery disease (2021)
  • Author(s): Itagaki Tadashi, Ebisawa Soichiro, Otagiri Kyuhachi, Kato Tamon, Miura Takashi, Kanzaki Yusuke, Abe Naoyuki, Yokota Daisuke, Yanagisawa Takashi, Senda Keisuke, Okina Yoshiteru, Wakabayashi Tadamasa, Oyama Yushi, Machida Keisuke, Takeuchi Takahiro, Saigusa Tatsuya, Motoki Hirohiko, Kitabayashi Hiroshi, Kuwahara Koichiro
  • Journal Title: Heart and Vessels Volume: 36 Issue: 12 Pages: 1830-1840
  • DOI: 10.1007/s00380-021-01883-2
  • Peer Reviewed / Open Access
• [Journal Article] Impact of Frailty and Age on Clinical Outcomes in Patients Who Underwent Endovascular Therapy (2021)
  • Author(s): Nishikawa Ken, Ebisawa Soichiro, Miura Takashi, Kato Tamon, Yusuke Kanzaki, Abe Naoyuki, Yokota Daisuke, Senda Keisuke, Yui Hisanori, Maruyama Shusaku, Nagae Ayumu, Sakai Takahiro, Okina Yoshiteru, Nakazawa Shun, Tsukada Shunichi, Saigusa Tatsuya, Okada Ayako, Motoki Hirohiko, Kagoshima Mitsuru, Kuwahara Koichiro
  • Journal Title: Journal of Endovascular Therapy Volume: Online ahead of print Issue: 6 Pages: 845-854
  • DOI: 10.1177/15266028211067729
  • Peer Reviewed
• [Journal Article] Prognostic ability of mid-term worsening renal function after percutaneous coronary intervention: findings from the SHINANO registry (2021)
  • Author(s): Okina Yoshiteru、Miura Takashi、Senda Keisuke、Taki Minami、Kobayashi Masanori、Kanai Masafumi、Okuma Yukari、Yanagisawa Takashi、Hashizume Naoto、Otagiri Kyuhachi、Shoin Kyoko、Watanabe Noboru、Ebisawa Soichiro、Karube Kenichi、Nakajima Hiroyuki、Saigusa Tatsuya、Miyashita Yusuke、Ikeda Uichi、Kuwahara Koichiro
  • Journal Title: Heart and Vessels Volume: Online ahead of print Issue: 10 Pages: 1496-1505
  • DOI: 10.1007/s00380-021-01837-8
  • Peer Reviewed
• [Journal Article] Early vascular response of ultra-thin bioresorbable polymer sirolimus-eluting stents assessed by optical frequency domain imaging: the EVALUATION study (2020)
  • Author(s): Miura Takashi、Ueki Yasushi、Senda Keisuke、Otagiri Kyuhachi、Tachibana Takahiro、Saigusa Tatsuya、Ebisawa Soichiro、Motoki Hirohiko、Ikeda Uichi、Kuwahara Koichiro
  • Journal Title: Cardiovascular Intervention and Therapeutics Volume: Online ahead of print Issue: 3 Pages: 281-288
  • DOI: 10.1007/s12928-020-00689-9
  • NAID: 40022621517
  • Peer Reviewed / Open Access
• [Presentation] Association between Calcification Biomarkers (Fibroblast Growth Factor 23, Osteoprotegerin, Fetuin-A) and Calcification of the Coronary Artery, Aorta, and Aortic Valve (2022)
  • Author(s): Keisuke Senda, Hidetsugu Yoda, Kazuma Masuda, Kyoko Shoin, Yasutaka Oguchi, Katsuyuki Aizawa, Chihiro Suzuki, Satoshi Yasukochi, Koichiro Kuwahara
  • Organizer: 第86回日本循環器学会学術集会
• [Presentation] 全身動脈および大動脈弁の石灰化と Fibroblast growth factor 23 (FGF-23) の関係 (2021)
  • Author(s): 千田啓介、依田英貢、増田一摩、正印恭子、小口泰尚、相澤克之、鈴木智裕、安河内聰、桑原宏一郎
  • Organizer: 第69回日本心臓病学会学術集会
• [Presentation] 単純X線写真における大動脈石灰化の半定量評価による 冠動脈石灰化スコアの予測 (2021)
  • Author(s): 千田啓介、依田英貢、増田一摩、正印恭子、小口泰尚、相澤克之、鈴木智裕、安河内聰、桑原宏一郎
  • Organizer: 第53回日本動脈硬化学会総会・学術集会
• [Presentation] Association of the Prognosis of Ankle-brachial Index Improvement 1 Year after Endovascular Therapy: From the I-PAD Registry (2021)
  • Author(s): 千田啓介、三浦崇、加藤太門、神崎佑介、阿部直之、横田大輔、柳澤聖、翁佳輝、若林禎正、小山由志、軽辺健一、板垣惟、正印恭子 、小口泰尚、相澤克之、麻生真一、鈴木智裕
  • Organizer: 第29回日本心血管インターベンション治療学会
• [Presentation] Association of the Prognosis of Ankle-brachial Index Improvement 1 Year after Endovascular Therapy: From the I-PAD Registry (2020)
  • Author(s): Keisuke Senda、Takashi Miura、Tamon Katoh、 Yusuke Kanzaki、Naoyuki Abe、Daisuke Yokota、 Takashi Yanagisawa、Yoshiteru Okina、Yushi Oyama、Kenichi Karube、Tadashi Itagaki、Kyoko Shouin、Yasutaka Oguchi、Katuyuki Aizawa、 Shinichi Asoh、Chihiro Suzuki
  • Organizer: 第84回日本循環器学会学術集会
• [Presentation] Differences in the Efficacy of Cilostazol on Target Lesions Treated with Endovascular Therapy: From the I-PAD Registry (2020)
  • Author(s): Keisuke Senda、Takashi Miura、Tamon Katoh、 Yusuke Kanzaki、Naoyuki Abe、Daisuke Yokota、 Takashi Yanagisawa、Yoshiteru Okina、Yushi Oyama、Kenichi Karube、Tadashi Itagaki、Kyoko Shouin、Yasutaka Oguchi、Katuyuki Aizawa、 Shinichi Asoh、Chihiro Suzuki
  • Organizer: 第84回日本循環器学会学術集会