各種薬剤溶出性ステント術後の傷害血管修復機転に関する研究

2012 Fiscal Year Annual Research Report

• Project/Area Number: 22590794
• Research Institution: Dokkyo Medical University
• Principal Investigator: 井上 晃男 獨協医科大学, 医学部, 教授 (20168454)
• Co-Investigator(Kenkyū-buntansha): 阿部 七郎 獨協医科大学, 医学部, 教授 (80275718) ; 田口 功 獨協医科大学, 医学部, 准教授 (80316570)
• Project Period (FY): 2010-04-01 – 2013-03-31
• Keywords: 臨床心血管病態学 / 分子血管病態学

Research Abstract

平成23年度に引き続き第二世代の薬剤溶出性ステント(DES)であるゾタロリムス溶出性ステント(ZES)とエベロリムス溶出性ステント(EES)における傷害血管修復機転を検討し、ベアメタルステント(BMS)との比較を行った。フローサイトメトリーによる末梢血血管内皮前駆細胞(EPC: CD34+/CD133+/CD45lowcell)数の評価では冠動脈ステント留置全38例(年齢70±9歳、BMS15例、ZES9例、EES14例)において留置前に比べ、7日目の変化率はBMS、ZES、EESの各群でそれぞれ74±59%、13±55% (P<0.05 vs BMS)、1±40% (P<0.001 vs BMS)であり、そのうち17例(BMS5例、ZES6例、EES6例)で光干渉断層法(OCT)による遠隔期(平均10か月)のステント表面の新生内膜被覆度の観察したところ、非被覆化率はそれぞれ2.4±4.0%、2.6±1.9%、41.6±25.6% (P<0.001 vs BMS)であった。そして7日目のEPC数の変化率と新生内膜非被覆化率との間には負の相関 (R=0.42, P<0.05)が見られた。また本年度は新たにin-vitroの検討を行った。健常例5例から末梢血幹細胞を抽出し、VEGFを含む内皮環境下での培養を行ったところCD31陽性血管内皮様細胞へと分化した。次にこれらの培養時にシロリムス、ゾタロリムス、エベロリムスの3薬を添加すると(0.01, 0.1, 1 nM)、コントロール(100%として)に比べ内皮様細胞への分化はシロリムス(各容量でそれぞれ28%, 19%, 2%)、ゾタロリムス(34%, 23%, 7%)、エベロリムス(44%, 47%, 4%)の順に抑制された。以上の結果から第二世代といえどもDES留置後の傷害血管の修復過程には問題があることが明らかとなった。

Current Status of Research Progress

Reason

24年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

24年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Cyclophilin A is a promising predictor of coronary artery disease. (2013)
  • Author(s): Taguchi I, Abe S, Inoue T
  • Journal Title: Circ J Volume: 77 Pages: 321-322
  • Peer Reviewed
• [Journal Article] Evaluation of serial changes in tissue characteristics during statin-induced plaque regression using virtual histology-intravascular ultrasound studies. (2013)
  • Author(s): Taguchi I, Oda K, Yoneda S, Kageyama M, Kanaya T, Toyoda S, Abe S, Node K, Inoue T
  • Journal Title: Am J Cardiol Volume: 111 Pages: 1246-1252
  • DOI: 10.1016/j.amjcard.2013.01.265.
  • Peer Reviewed
• [Journal Article] Irbesartan, an angiotensin receptor blocker, exhibits metabolic, anti-inflammatory and antioxidative effects in patients with high-risk hypertension. (2013)
  • Author(s): Taguchi I, Toyoda S, Takano K, Arikawa T, Kikuchi M, Ogawa M, Abe S, Node K, Inoue T
  • Journal Title: Hypertens Res Volume: in press Pages: in press
  • DOI: 10.1038/hr.2013.3.
  • Peer Reviewed
• [Journal Article] Late phase inflammatory response as a feature of in-stent restenosis after drug-eluting stent implantation. (2013)
  • Author(s): Yoneda S, Abe S, Kanaya T, Oda K, Nishino S, Kageyama M, Taguchi I, Masawa N, Inoue T
  • Journal Title: Coron Artery Dis Volume: in press Pages: in press
  • Peer Reviewed
• [Journal Article] The late phase inflammatory response after drug-eluting stent implantation. (2013)
  • Author(s): Taguchi I, Yoneda S, Abe S, Toyoda S, Nasuno T, Nishino S, Kageyama M, Tokura M, Ogawa M, Node K, Inoue T
  • Journal Title: Heart Vessels Volume: in press Pages: in press
  • Peer Reviewed
• [Journal Article] Inflammation and impaired wound healing after zotarolimus-eluting stent implantation (2012)
  • Author(s): Yoneda S, Abe S, Taguchi I, Masawa N, Inoue K, Inoue T
  • Journal Title: Cardiovasc Pathol Volume: 21 Pages: 511-514
  • DOI: DOI:10.1016/j.carpath.2012.01.003
  • Peer Reviewed
• [Journal Article] Does direct inhibition bring direct benefit? (2012)
  • Author(s): Abe S, Taguchi I, Inoue T
  • Journal Title: Circ J Volume: 76 Pages: 1326
  • DOI: 10.1253/circj.CJ-11-0407
  • Peer Reviewed
• [Journal Article] Pathological features of in-stent restenosis after sirolimus-eluting stent versus bare metal stent placement. (2012)
  • Author(s): Abe S, Yoneda S, Kanaya T, Oda K, Nishino S, Kageyama M, Taguchi I, Masawa N, Inoue T
  • Journal Title: Cardiovasc Pathol Volume: 21 Pages: e19-e22
  • DOI: 10.1016/j.carpath.2011.02.003.
  • Peer Reviewed
• [Presentation] Inflammation in vascular injury and repair after stenting -novel issues in DES era and our approach to the 'stentless' PCI-.
  • Author(s): Inoue T
  • Organizer: NSE up-to-date ～the stentless coronary angioplasty～
  • Place of Presentation: Bangkok, Thailand
  • Invited
• [Presentation] Stentless balloon angioplasty with a novel balloon catheter,lacrosse non-slip element balloon
  • Author(s): Kageyama M, Taguchi I, Tokura M, Nishiyama Y, Nasuno T, Nishino S, Yoneda S, Oda K, Abe S, Inoue T
  • Organizer: The 21th Annual Meeting of the Japanese Association of Cardiovascular Intervention and Therapeutics
  • Place of Presentation: Niigata, Japan
• [Presentation] Inflammatory response at late phase after drug-eluting stent implantation
  • Author(s): Yoneda S, Oda K, Nasuno T, Nishino S, Kageyama M, Tokura M, Taguchi I, Abe S, Inoue T
  • Organizer: The 21th Annual Meeting of the Japanese Association of Cardiovascular Intervention and Therapeutics
  • Place of Presentation: Niigata, Japan
• [Presentation] Matrix metalloproteinase-9 might contribute to mobilization of bone marrow-derived cells after coronary stent implantation.
  • Author(s): Nasuno T, Taguchi I, Kikuchi M, Toyoda S, Abe S, Node K, Inoue T
  • Organizer: 19th Asia Pacific Congress of Cardiology
  • Place of Presentation: Pattya, Thailand
• [Presentation] Sulfatides are associated with neointimal thickning after vascular injury.
  • Author(s): Nasuno T, Taguchi I, Kageyama M, Toyoda S, Kikuchi M, Abe S, Kyogeshima M, Node K, Inoue T
  • Organizer: 19th Asia Pacific Congress of Cardiology
  • Place of Presentation: Pattya, Thailand
• [Presentation] Serial change in tissue chatacteristics during plaque regression process by statins-virtual histology intravascular ultrasound evaluation.
  • Author(s): Kageyama M, Taguchi I, Kikuchi M, Toyoda S, Abe S, Node K, Inoue T
  • Organizer: 19th Asia Pacific Congress of Cardiology
  • Place of Presentation: Pattya, Thailand
• [Presentation] Stentless coronary angioplasty using non slip elements balloon is acceptable strategy in selected patients.
  • Author(s): Kageyama M, Taguchi I, Oda K, Kikuchi M, Toyoda S, Abe S, Node K, Inoue T
  • Organizer: 19th Asia Pacific Congress of Cardiology
  • Place of Presentation: Pattya, Thailand
• [Presentation] Catheter-based observation of blood nitric oxide levels in forearm artery.
  • Author(s): Abe S, Tokura M, Nishiyama Y, Kageyama M, Nishino S, Nasuno T, Taguchi I, Inoue T
  • Organizer: The 77th Annual Scientific Meeting of the Japanese Circulation Society
  • Place of Presentation: Yokohama, Japan