All trans retinoic acid alleviates coronary stenosis by regulating smooth muscle cell function in a mouse model of Kawasaki disease

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.

Automated summary

The study demonstrated that all-trans-retinoic acid (atRA) has a significant inhibitory effect on coronary artery stenosis in patients with Kawasaki disease. By suppressing smooth muscle cell migration, atRA effectively alleviates CA inflammation and reduces the incidence of CA stenosis.