Author + information
- Received September 17, 2019
- Revision received October 21, 2019
- Accepted October 21, 2019
- Published online February 24, 2020.
- Saki Hirakata, MDa,
- Hiroki Aoki, MD, PhDb,∗ (, )
- Satoko Ohno-Urabe, MD, PhDa,
- Michihide Nishihara, MD, PhDa,
- Aya Furusho, MD, PhDa,
- Norifumi Nishida, MDa,
- Sohei Ito, MDa,
- Makiko Hayashi, MDa,
- Hideo Yasukawa, MD, PhDa,
- Tsutomu Imaizumi, MD, PhDc,
- Sinichi Hiromatsu, MD, PhDd,
- Hiroyuki Tanaka, MD, PhDd and
- Yoshihiro Fukumoto, MD, PhDa
- aDivision of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Japan
- bCardiovascular Research Institute, Kurume University, Kurume, Japan
- cInternational University of Health and Welfare, Fukuoka, Japan
- dDivision of Cardiovascular Surgery, Department of Surgery, Kurume University School of Medicine, Kurume, Japan
- ↵∗Address for correspondence:
Dr. Hiroki Aoki, Cardiovascular Research Institute, Kurume University, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan.
• Stat3, a major signaling molecule for proinflammatory cytokines including IL-6, was activated both in inflammatory cells and in SMC in the aortic walls of human AD and mouse AD model.
• SMC-specific deletion of Socs3 enhanced Stat3 activation in SMC, induced moderate proinflammatory response in the aortic walls, and ameliorated AD in mice.
• SmSocs3-KO aortas showed increases in fibroblasts, adventitial collagen fibers, and tensile strength of the aortic walls.
• IL-6-stimulated SMC in culture secreted humoral factor(s) that promoted proliferative response of fibroblasts.
Aortic dissection (AD) is the acute destruction of aortic wall and is reportedly induced by inflammatory response. Here we investigated the role of smooth muscle Socs3 (a negative regulator of Janus kinases/signal transducer and activator of transcription signaling) in AD pathogenesis using a mouse model generated via β-aminopropionitrile and angiotensin II infusion. Socs3 deletion specifically in smooth muscle cells yielded a chronic inflammatory response of the aortic wall, which was associated with increased fibroblasts, reinforced aortic tensile strength, and less-severe tissue destruction. Although an acute inflammatory response is detrimental in AD, smooth muscle-regulated inflammatory response seemed protective against AD.
This work was funded, in part, by Grant-in-Aid for Young Scientists 24791398 and 26861116 (awarded to Dr. Hirotaka), Grant-in-Aid for Scientific Research 16K10669 (awarded to Dr. Hirotaka), 21390367, 24390334, 24659640, 26670621, and 16H05428 (awarded to Dr. Aoki) from Japanese Society for the Promotion of Science; grants from the Daiichi Sankyo Foundation of Life Science, the Uehara Memorial Foundation (awarded to Dr. Aoki), the Vehicle Racing Commemorative Foundation (awarded to Dr. Aoki), and Bristol-Myers Squibb (awarded to Dr. Aoki); and Take a New Challenge for Drug Discovery, or TaNeDS, grants from Daiichi Sankyo (awarded to Dr. Aoki). The 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 September 17, 2019.
- Revision received October 21, 2019.
- Accepted October 21, 2019.
- 2020 The Authors