Author + information
- Received October 11, 2019
- Revision received January 8, 2020
- Accepted January 8, 2020
- Published online April 27, 2020.
- Mitsumasa Okano, MDa,
- Tetsuya Hara, MD, PhDa,∗ (, )
- Makoto Nishimori, MDa,
- Yasuhiro Irino, PhDb,
- Seimi Satomi-Kobayashi, MD, PhDa,
- Masakazu Shinohara, MD, PhDc,
- Ryuji Toh, MD, PhDb,
- Farouc A. Jaffer, MD, PhDd,
- Tatsuro Ishida, MD, PhDa and
- Ken-ichi Hirata, MD, PhDa,b
- aDivision of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- bDivision of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- cDivision of Epidemiology, Kobe University Graduate School of Medicine, Kobe, Japan
- dCardiovascular Research Center, Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts
- ↵∗Address for correspondence:
Dr. Tetsuya Hara, Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 6500017, Japan.
• We established a novel clinically relevant murine DVT model at femoral/saphenous vein induced by flow restriction and light illumination.
• Our model newly succeeded in inducing DVT in a valve pocket and enabled spontaneous pulmonary embolism of fibrin-rich thrombus from lower extremity vein, reproducing the clinical VTE scenario.
• This model is suitable for motion-free in vivo high-resolution imaging of fibrin-rich DVT development and organization using 2-photon microscopy, enabling the real-time imaging of migration of platelets and leukocytes into the erythrocyte-rich DVT.
This work established a new murine venous thromboembolism (VTE) model. This model has multiple novel features representing clinical VTE that include the following: 1) deep venous thrombosis (DVT) was formed and extended in the long axis of femoral/saphenous vein; 2) thrombus was formed in a venous valve pocket; 3) deligation of suture-induced spontaneous pulmonary emboli of fibrin-rich DVT; and 4) cardiac motion-free femoral/saphenous vein allowed high-resolution intravital microscopic imaging of fibrin-rich DVT. This new model requires only commercially available epifluorescence microscopy. Therefore, this model has significant potential for better understanding of VTE pathophysiology.
This study was supported by Grants-In-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (19K08516), the Mochida Memorial Foundation for Medical and Pharmaceutical Research, and National Institutes of Health’s National Heart, Lung, and Blood Institute grant R01HL137913. Drs. Toh and Irino have reported that the Division of Evidence-based Laboratory Medicine was established by an endowment fund from the Sysmex Corporation. Dr. Jaffer has received research grants from Canon and Siemens; has served as a proctor for and on the Advisory Boards of Abbott Vascular and Boston Scientific; has consulted for Acrostak; and is a shareholder in Intravascular Imaging, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received October 11, 2019.
- Revision received January 8, 2020.
- Accepted January 8, 2020.
- 2020 The Authors