Department of Vascular Physiology

 

Member

Director	Yoshikazu Nakaoka
Laboratory Chief	Makoto Okazawa Masaki Mori
Staff Scientist	Atsushi Nakano Tomohiko Ishibashi Tadakatsu Inagaki
Postdoctoral Fellow	Saori Mizushima Ryotaro Asano Xin Ding Shuichi Tonomura Yui Kotani Akiko Yamagishi Yuko Taira Kaori Higashi
Research Assistant	Noriko Maedera Toru Nakajima Mika Ejiri Kokone Hata Nao Araki
Data Manager	Yuko Iwai Masayo Kusumoto

 

Research

Aim of our research group is to understand the molecular mechanisms and to develop novel therapeutic strategies for intractable cardiovascular diseases.
We have been interested in the molecular pathogenesis of intractable vascular diseases such as pulmonary arterial hypertension (PAH) and Takayasu arteritis (TAK), especially focusing on inflammatory cytokines. In PAH animal models, we have found that both IL-6 and IL-21 have crucial roles in the pathogenesis of PAH. In addition, we recently reported that a transcriptional factor aryl hydrocarbon receptor (AHR) plays a critical role in the pathogenesis of PAH. On the other hand, we have been examining the efficacy of IL-6 blockade in patients with TAK. Through clinical trials, we could get the approval of tocilizumab, an IL-6 receptor monoclonal antibody, for treatment of TAK from the Japanese government.
We are currently interested in the origin of inflammation of various cardiovascular diseases. We have been investigating the role of gut microbiome in the pathogenesis of cardiovascular diseases including PAH, TAK, stroke, heart failure and so on. We would like to develop novel therapeutic and diagnostic strategies for cardiovascular diseases through elucidating the molecular linkages between gut microbiome and inflammation.

 

Publication

1.  Manabe Y, Ishibashi T, Asano R, Tonomura S, Maeda Y, Motooka D, Ueda J, Yanagawa M, Edamoto-Taira Y, Chikaishi-Kirino T, Masaki T, Inagaki T, Nakamura S, Katada Y, Okazawa M, Narazaki M, Ogo T, Kumanogoh A, Nakaoka Y*. Gut Dysbiosis is associated with aortic aneurysm formation and progression in Takayasu arteritis. Arthritis Res Ther. 2023. 25(1); 46; doi:10.1186/s13075-023-03031-9.
2. Yaku A, Inagaki T, Asano R, Okazawa M, Mori H, Sato A, Hia F, Masaki T, Manabe Y, Ishibashi T, Vandenbon A, Nakatsuka Y, Akaki K, Yoshinaga M, Uehata T, Mino T, Ishibashi-Ueda H, Morinobu A, Tsujimura T, Ogo T, Nakaoka Y*, Takeuchi O*. Regnase-1 prevents pulmonary arterial hypertension via mRNA degradation of Interleukin-6 and Platelet-Derived Growth Factor in alveolar macrophages. Circulation.
   2022 Sep 27;146(13):1006-1022 (*equal contribution, *co-correspondence)
3. Nakaoka Y, Yanagawa M, Hata A, Yamashita K, Okada N, Yamakido S, Hayashi H, Jayne D. Vascular imaging of patients with refractory Takayasu arteritis treated with tocilizumab: post hoc analysis of a randomized controlled trial. Rheumatology (Oxford). 2021 Sep 16: keab684. doi: 10.1093/rheumatology/keab684.
4. Masaki T, Okazawa M, Asano R, Inagaki T, Ishibashi T, Yamagishi A, Mizushima S, Nishimura M, Manabe Y, Ishibashi-Ueda H, Shirai M, Tsuchimochi H, Pearson JT, Kumanogoh A, Sakata Y, Ogo T, Kishimoto T, Nakaoka Y. Aryl hydrocarbon receptor is essential for the pathogenesis of pulmonary arterial hypertension. Proc Natl Acad Sci U S A. 118(11): e2023899118, 2021
5. Inagaki T, Pearson JT, Tsuchimochi H, Schwenke DO, Saito S, Higuchi T, Masaki T, Umetani K, Shirai M, Nakaoka Y. Evaluation of right coronary vascular dysfunction in severe pulmonary hypertensive rats using synchrotron radiation microangiography. Am J Physiol Heart Circ Physiol. 2021 Mar 1; 320(3):H1021-H1036.
6. Nakaoka Y, Isobe M, Tanaka Y, et al. Long-term efficacy and safety of tocilizumab in refractory Takayasu arteritis: final results of the randomised controlled phase 3 TAKT study. Rheumatology (Oxford). 2020 Sep 1;59(9):2427-2434.
7. Mori H, Ishibashi T, Inagaki T, Okazawa M, Masaki T, Asano R, Manabe Y, Ohta-Ogo K, Narazaki M, Ishibashi-Ueda H, Kumanogoh A, Nakaoka Y. Pristane/Hypoxia Mouse as a Novel Model of Pulmonary Hypertensin Reflecting Inflammation and Fibrosis. Circ J. 2020 Jun 25;84(7):1163-1172.

last updated : 2024/03/15