Vascular endothelial growth factor-a in Lactobacillus casei cell wall extract-induced coronary arteritis of a murine model

Abstract

Background: Vascular endothelial growth factor (VEGF) is associated with Kawasaki disease (KD), the most commonly acquired heart disease in developed countries. This study investigated the involvement of VEGF-A expression and its related signaling pathway in Lactobacillus casei cell wall extract (LCWE)-induced murine coronary artery lesions (CALs), and analyzed this in regard to the inhibition of CALs by spleen tyrosine kinase (Syk). Methods and Results: Wild-type BALB/C mice were intraperitoneally injected with LCWE (1 mg/ml) to induce CALs. The aortic roots, ventricular myocardium, peripheral blood leukocytes (PBLs), spleen, liver, kidneys, and lungs were analyzed for VEGF-A expression. Phosphate buffered saline (PBS)-, lipopolysaccharide (LPS)-, and zymosan-treated mice served as controls, and an oral Syk inhibitor served as an arteritis-ameliorated reagent. In aortic roots and PBLs, LCWE induced an early upregulation and a late downregulation of VEGF-A expression. No differential VEGFA expression was observed in the other organs. Most importantly, Syk inhibition significantly attenuated the LCWEinduced expression of VEGF-A, dimethylarginine dimethylaminohydrolase (DDAH)-1, and endothelial nitric oxide synthase in aortic roots. However, LCWE-induced aortic DDAH-2 expression remained higher, despite Syk inhibition. Conclusions: Local VEGF-A and its signaling pathway are associated with the development of LCWE-induced CALs. Therefore, the clinical correlation between VEGF and human KD and the role of the VEGF-A regulation and signaling pathway in murine CALs warrant further investigation.