Three-dimensional multilayers of smooth muscle cells as a new experimental model for vascular biology

2013 Fiscal Year Final Research Report

• Project/Area Number: 24659100
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General physiology
• Research Institution: Yokohama City University
• Principal Investigator: YOKOYAMA Utako 横浜市立大学, 医学部, 講師 (70404994)
• Co-Investigator(Renkei-kenkyūsha): ISHIKAWA Yoshihiro 横山市立大学, 医学研究科, 教授 (40305470) ; ICHIKAWA Yasuhiro 横山市立大学, 医学部, 助教 (10555121)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Keywords: 循環器・高血圧 / 生理学 / ナノバイオ / 細胞・組織 / 三次元培養 / 弾性線維 / 動脈硬化

Research Abstract

Elastic fiber formation is disrupted with age and by health conditions including aneurysms and atherosclerosis. Despite considerable progress in the understanding of elastogenesis using the planar culture system and genetically modified animals, it remains difficult to restore elastic fibers in diseased vessels. To further study the molecular mechanisms, we created in vitro three-dimensional vascular constructs. Three-dimensional cellular multilayers (3DCMs), which consisted of seven layers of neonatal rat aortic SMCs cultured in 1% fetal bovine serum in DMEM medium, exhibited layered elastic fibers and differentiated smooth muscle cell phenotype within seven days of being in a static culture condition. Furthermore, infiltration of THP-1-derived macrophages decreased the surrounding elastic fiber formation in 3DCMs. 3DCMs may offer a new experimental vascular model to explore pharmacological therapeutic strategies for abnormal vascular remodeling.

Research Products

• [Journal Article] Three-Dimensional Multilayers of Smooth Muscle Cells as a New Experimental Model forVascular Elastic Fiber Formation Studies (2014)
  • Author(s): Ishiwata R, Yokoyama U, Matsusaki M, Asano Y, Kadowaki K, Ichikawa Y, Umemura M,Fujita T, Minamisawa S, Shimoda H, Akashi M, and Ishikawa Y
  • Journal Title: Atherosclerosis Volume: 233 Pages: 590-600
  • DOI: 10.1016/j.atherosclerosis.2014.01.045
  • Peer Reviewed
• [Journal Article] Prostaglandin E_2 inhibits elastogenesis in the ductus arteriosus via EP4 signaling (2014)
  • Author(s): Yokoyama U, Minamisawa S, Shioda A, Ishiwata R, Jin MH, Masuda M, Asou T, Sugimoto Y, Aoki H, Nakamura T, Ishikawa Y
  • Journal Title: Circulation Volume: 129 Pages: 487-96
  • DOI: 10.1161/CIRCULATIONAHA.113.004726
  • Peer Reviewed
• [Journal Article] The prostanoid EP4 receptorand its signaling pathway (2013)
  • Author(s): Y okoyama U, Iwatsubo K, Umemura M, Fujita T, Ishikawa Y
  • Journal Title: Pharmacol Rev Volume: 65 Pages: 1010-52
  • DOI: 10.1124/pr.112.007195
  • Peer Reviewed
• [Journal Article] 動脈瘤とPGE_2 (2013)
  • Author(s): 横山詩子,金美花,石川義弘
  • Journal Title: 遺伝子医学MOOK Volume: 24 Pages: 296-300
  • URL: http://www.medicaldo.co.p/gene/mook.no24.html
• [Journal Article] Inhibition of EP4 signaling Attenuates Aortic Aneurysm Formation (2012)
  • Author(s): Yokoyama U, Ishiwata R, Jin MH, Kato Y, Suzuki O, Jin H, Ichikawa Y, Kumagaya S, Katayama Y, Fujita T, Okumura S, Sato M, Sugimoto Y, Aoki H, Suzuki S, Masuda M, Minamisawa S, Ishikawa Y
  • Journal Title: PLoS ONE Volume: 7 Pages: e36724
  • DOI: 10.1371/journal.pone.0036724
  • Peer Reviewed
• [Journal Article] Pharmacological Stimulation of Type 5 Adenylyl Cyclase Stabilizes Heart Rate under both Microgravity and Hypergravity induced by Parabolic Flight (2012)
  • Author(s): Bai Y, Tsunematsu T, Jiao Q, Ohnuki Y, Mototani Y, Shiozawa K, Jin MH, Cai W, Jin HL, Fujita T, Ichikawa Y, Suita K, Kurotani R, Yokoyama U, Sato M, Iwatsubo K, Ishikawa Y, Okumura S
  • Journal Title: J Pharmacol Sci Volume: 119 Pages: 381-9
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22850613
  • Peer Reviewed
• [Journal Article] Inhibition of Phosphodiesterase Type 3 Dilates the Rat Ductus Arteriosus without Inducing Intimal Thickening (2012)
  • Author(s): I chikawa Y, Yokoyama U, Iwamoto M, Oshikawa J, Okumura S, Sato M, Yokota S, Masuda M, Asou T, Isikawa Y
  • Journal Title: Circ J Volume: 76 Pages: 2456-64
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/22785618
  • Peer Reviewed
• [Journal Article] Low-dose Thromboxane A2 Receptor Stimulation Promotes Closure of the Rat Ductus Arteriosus with Minimal Adverse Effects (2012)
  • Author(s): Yokota T, Aida T, Ichikawa Y, Fujita T, Yokoyama U, Minamisawa S
  • Journal Title: Pediatr Res Volume: 72 Pages: 129-36
  • DOI: 10.1371/journal.pone.0094895
  • Peer Reviewed
• [Journal Article] Effect of ascorbic acid on reactive oxygen species Production in chemotherapy and hyperthermia in prostate cancer cells (2012)
  • Author(s): Fukumura H, Sato M, Kezuka K, Sato I, Feng X, Okumura S, Fujita T, Yokoyama U, Eguchi H, Ishikawa Y, Saito T
  • Journal Title: J Physiol Sci Volume: 62 Pages: 251-7
  • DOI: 10.1007/s12576-012-0204-0
  • Peer Reviewed
• [Journal Article] Cyclic AMP and Epac in the Regulation of tissue fibrosis (2012)
  • Author(s): Insel PA, Murray F, Yokoyama U, Romano S,Yun H, Brown L, Snead A, Lu D, Aroonsakool N
  • Journal Title: Br J Pharmacol Volume: 166 Pages: 447-56
  • DOI: 10.1111/j.1476-5381.2012.01847.x
  • Peer Reviewed
• [Journal Article] Akashi Morphological and Histological Evaluations of 3D-Layered Blood Vessel Constructs Prepared by Hierarchical Cell Manipulation (2012)
  • Author(s): Matsusaki M, Kadowaki K, Adachi E, Sakura T, Yokoyama U, Ishikawa Y
  • Journal Title: J Biomater Sci Polym Ed Volume: 23 Pages: 63-79
  • DOI: 10.1163/092050610X541953
  • Peer Reviewed
• [Journal Article] 三次元血管モデルを用いた動脈硬化性疾患の機序解明Elucidation of Molecular Mechanisms of Atherosclerosis by Three-Dimensional (3D)-Layered Blood Vessel Constructs (2012)
  • Author(s): 横山詩子、石渡遼、大島登志男、南沢享、石川義弘
  • Journal Title: 科学と工業 Volume: 86 Pages: 329-35
  • URL: http://www.osakaira.com/kagaku_86.html
• [Presentation] Molecular mechanisms of the regulation of vascular elastic fiber formation and development of a new 3D vascular model (2013)
  • Author(s): Yokoyama U
  • Organizer: The 36^<th> Annual Meeting of the Molecular Biology Society of Japan
  • Place of Presentation: Kobe
  • Year and Date: 20131203-06
  • Invited
• [Presentation] Molecular Mechanisms of Dynamic Cardiovascular Adaptation from Fetal to Neonatal Life (2013)
  • Author(s): Yokoyama U
  • Organizer: The 90^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Tokyo
  • Year and Date: 20130327-29
  • Invited
• [Presentation] Proteomic analysis identified prostaglandin E2-induced proteins in tissues from patients with aortic aneurysm (2013)
  • Author(s): Ishiwata R, Yokoyama U, Arakawa N, Nomura A, Oshima T, Minamisawa S, Ishikawa Y
  • Organizer: The 90^<th> Annual Meeting of the Physiological Society of Japan
  • Place of Presentation: Tokyo
  • Year and Date: 20130327-29
• [Presentation] 血管弾性線維形成の機序解明に向けた三次元血管壁組織の開発 (2013)
  • Author(s): 横山詩子
  • Organizer: 第2回三次元生体組織構築公開シンポジウム-世界基準へのチャレンジ-
  • Place of Presentation: 東京
  • Year and Date: 2013-11-28
  • Invited
• [Presentation] プロスタグランディンEによる血管弾性線維の制御メカニズムと新たな三次元血管モデルの可能性 (2013)
  • Author(s): 横山詩子
  • Organizer: 第18回NCVC研究者交流会
  • Place of Presentation: 大阪(国立循環器病研究所セミナー)
  • Year and Date: 2013-09-27
• [Presentation] Rat Smooth Muscle Cells within Three Dimensional Cellular Multilayers Exhibit Contractile Phenotypes and Layered Elastic Fiber (2012)
  • Author(s): Ishiwata R, Yokoyama U, Kadowaki K, Matsusaki M, Akashi M, Ishikawa Y, Minamisawa S
  • Organizer: The 8^<th> Congress of Asian Society for Pediatric Research
  • Place of Presentation: Seoul, Korea
  • Year and Date: 20120517-19
• [Presentation] 動脈硬化性疾患の機序解明にむけた三次元血管モデルの開発 (2012)
  • Author(s): 横山詩子
  • Organizer: 三次元生体組織構築公開シンポジウム-世界基準へのチャレンジ-
  • Place of Presentation: 東京
  • Year and Date: 2012-11-28
  • Invited
• [Presentation] プロスタグランジンEシグナルと弾性線維形成―動脈管閉鎖や大動脈瘤形成への関与 (2012)
  • Author(s): 横山詩子
  • Organizer: 医学研究の基礎を語り合う集いTokyo Heart Development Club
  • Place of Presentation: 東京
  • Year and Date: 2012-06-25
  • Invited
• [Book] Nanomedicine and Nanotoxicology (2014)
  • Author(s): Yokoyama U, Ishikawa Y
  • Total Pages: 8
  • Publisher: Springer
• [Book] Congenital Heart Disease - Selected Aspects (2012)
  • Author(s): Minamisawa S, Yokoyama U
  • Total Pages: 348
  • Publisher: InTech
• [Remarks] ホームページ:横浜市立大学医学部循環制御医学
  • URL: http://www-user.yokohama-cu.ac.jp/~seiri1
• [Patent(Industrial Property Rights)] 三次元組織体及びその製造方法 (2013)
  • Inventor(s): 明石満、松崎典弥、石川義弘、横山詩子
  • Industrial Property Rights Holder: 明石満、松崎典弥、石川義弘、横山詩子
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2013-212966
  • Filing Date: 2013-10-10