The Notch1/Jagged1 Pathway is Involved in the Development of Rheumatic Heart Disease

Abstract

Objective: To investigate the role of Notch1/Jagged1 in the development of rheumatic heart disease (RHD). Methods: 35 RHD patients who underwent mitral valve replacement, 35 healthy volunteers, and 10 dead persons by traffic accident were selected in the present study. The morphological changes of mitral valve in the RHD patients were observed. The mRNA and protein levels of Notch1/Jagged1 in the mitral valves were assayed using real-time PCR and western blot, respectively. The location and distribution of Notch1/Jagged1 proteins in the mitral valves were analyzed by immunohistochemistry. Flow cytometry (FCM) was used to measure the positive ratios of Notch 1/Jagged1 in isolated peripheral mononuclear cells. Results: Histomorphology data showed that the fusion of commissures, cusps, and chordae tendinea resulted in thickened, shortened and inflexible alterations of the mitral valves. Real-time PCR and western blot assays revealed that the mRNA and protein levels of Notch1/Jagged1 were significantly higher in the impaired mitral valves of the RHD patients compared to controls. Immunohistochemistry revealed that Notch1/Jagged1 proteins were mainly located in the cytoplasm of fibroblasts in the mitral valves. The positive ratio of Jagged1 in peripheral mononuclear cells in the RHD patients was significantly elevated compared to the controls. Conclusion: Notch1/Jagged1 expression in the damaged mitral valves of the RHD patients is significantly increased compared to controls. Meanwhile, the positive expression ratio of Jagged1 in the peripheral mononuclear cells of the RHD patients is markedly up regulated. In summary, the Notch1/Jagged1 pathway correlates with the development of RHD.