Division of Infectious Diseases and Immunology, Allergy, Saitama Children's Medical Center, 1-2 Shintoshin Chuou-ku Saitama-shi, Saitama, 330-8777, Japan.
Division of Clinical Research, Saitama Children's Medical Center, Saitama, Japan.
Sci Rep. 2021 Jul 5;11(1):13856. doi: 10.1038/s41598-021-93459-3.
Coronary artery (CA) stenosis is a detrimental and often life-threatening sequela in Kawasaki disease (KD) patients with coronary artery aneurysm (CAA). Therapeutic strategies for these patients have not yet been established. All-trans-retinoic acid (atRA) is a modulator of smooth muscle cell functions. The purpose of this study was to investigate the effect of atRA on CA stenosis in a mouse model of KD. Lactobacillus casei cell wall extract (LCWE) was intraperitoneally injected into 5-week-old male C57BL/6 J mice to induce CA stenosis. Two weeks later, the mice were orally administered atRA (30 mg/kg) 5 days per week for 14 weeks (LCWE + atRA group, n = 7). Mice in the untreated group (LCWE group, n = 6) received corn oil alone. Control mice were injected with phosphate-buffered saline (PBS, n = 5). Treatment with atRA significantly suppressed CA inflammation (19.3 ± 2.8 vs 4.4 ± 2.8, p < 0.0001) and reduced the incidence of CA stenosis (100% vs 18.5%, p < 0.05). In addition, atRA suppressed the migration of human coronary artery smooth muscle cells (HCASMCs) induced by platelet-derived growth factor subunit B homodimer (PDGF-BB). In conclusion, atRA dramatically alleviated CA stenosis by suppressing SMC migration. Therefore, it is expected to have clinical applications preventing CA stenosis in KD patients with CAA.
冠状动脉（CA）狭窄是川崎病（KD）患者伴冠状动脉瘤（CAA）的一种有害且常危及生命的后遗症。目前尚未确定这些患者的治疗策略。全反式视黄酸（atRA）是平滑肌细胞功能的调节剂。本研究旨在探讨 atRA 对 KD 小鼠模型 CA 狭窄的影响。将干酪乳杆菌细胞壁提取物（LCWE）腹腔注射至 5 周龄雄性 C57BL/6J 小鼠以诱导 CA 狭窄。2 周后，每周 5 天给予 atRA（30mg/kg）口服治疗 14 周（LCWE+atRA 组，n=7）。未治疗组（LCWE 组，n=6）给予玉米油。对照组小鼠给予磷酸盐缓冲液（PBS，n=5）。atRA 治疗显著抑制 CA 炎症（19.3±2.8 比 4.4±2.8，p<0.0001）和减少 CA 狭窄发生率（100%比 18.5%，p<0.05）。此外，atRA 抑制血小板衍生生长因子亚基 B 同二聚体（PDGF-BB）诱导的人冠状动脉平滑肌细胞（HCASMC）迁移。总之，atRA 通过抑制 SMC 迁移显著缓解 CA 狭窄。因此，有望在伴有 CAA 的 KD 患者中预防 CA 狭窄的临床应用。
