Vascular Endothelial Growth Factor-A in Lactobacillus Casei Cell Wall Extract-Induced Coronary Arteritis of a Murine Model

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概要

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• 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 (1mg/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 VEGF-A expression was observed in the other organs. Most importantly, Syk inhibition significantly attenuated the LCWE-induced 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.

• 一般社団法人 日本循環器学会の論文

著者

• Huang Li-tung

  Department Of Neurology Harvard Medical School Center For Research In Pediatric Epilepsy Children&ap

• Sheen Jiunn-ming

  Department Of Pediatrics Chang Gung Memorial Hospital-kaohsiung Medical Center College Of Medicine Chang Gung University

• YANG Kuender

  Department of Medical Research, Show Chwan Memorial Hospital in Chang Bing

• TAIN You-Lin

  Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, College of Medicine

• Lin I-Chun

  Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine

• Chou Ming-Huei

  Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University

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