All-trans-Retinoic Acid Alleviates Coronary Stenosis by Regulating the Migration of Smooth Muscle Cells in a Mouse Model of Kawasaki Disease

Abstract

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/6J 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.