Abstract
Background: Along with cell infiltration, exacerbated damage to the extracellular matrix (ECM) plays a major role in the development of coronary artery lesions in Kawasaki disease. Known for their antihypertensive effects, angiotensin receptor blockers (ARB) also act to suppress ECM damage; however, there are no reports at present regarding the efficacy of ARB for Kawasaki disease.
Methods: Four-week-old male C57/BL6 mice were intraperitoneally injected with 0.5 mg Lactobacillus casei cell wall extract (LCWE group; n = 10) or Phosphate-Buffered Saline (PBS group; n = 10). As a treatment group (LCWE + ARB group, n = 10), mice with intraperitoneal injection of LCWE were fed ARB-containing water (100 mg/l). Four weeks after the administration of LCWE, the degree of vasculitis was histologically evaluated. Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and interleukin-6 (IL-6) mRNA expressions at the aortic root were also studied using real-time polymerase chain reactions (PCR; n = 5).
Results: Histological examination revealed that LCWE-induced coronary arteritis was ameliorated by ARB as shown by decreased mononuclear cell infiltration and activated macrophage infiltration. Consistent with that result, real-time PCR demonstrated that increased mRNA expressions of MMP-9 and IL-6 in the LCWE group were slightly ameliorated by ARB administration.
Conclusion: ARB inhibits coronary arteritis via a mechanism that includes suppression of activated macrophages in a murine model of Kawasaki disease. Future therapeutic intervention with ARB as a rational drug is anticipated for Kawasaki disease.
