فهرست نشریات علمی دسترسی آزاد ایران

Background and Objectives: Lipopolysaccharide (LPS) has been previously reported to interact with Notch proteins to augment the osteogenic response of toll-like receptor 4 and induce calcification of valvular interstitial cells (VICs), leading to the development of calcified aortic valve disease. This study aimed to investigate the role and mechanisms of Notch 2 in VICs calcification.   Methods: Human VICs were cultured in a calcification medium and stimulated with LPS. The LPS-treated VICs were further divided into subgroups by adding the following reagents: Notch 2 specific inhibitor DAPT and DLL4, and the JAK/STAT-specific inhibitor GLPG0634. Calcification was assessed by von Kossa staining and expression of bone morphogenetic protein (BMP)-2 and BMP-4. Immunofluorescence staining was performed to determine the localization of Notch 2 Western blotting was performed to detect the expression of related proteins.   Results: LPS treatment significantly increased the number of calcified nodules and upregulated the expression of Notch 2, DLL4, Notch intracellular domain (NICD), BMP-2, and BMP-4. The addition of DAPT significantly inhibited the formation of calcified nodules and downregulated LPS-induced expression of BMP-2 and BMP-4 caused by LPS; however, DLL4 supplementation had the opposite effect. Furthermore, DAPT significantly blocked the phosphorylation of JAK/STAT, and treatment with the JAK/STAT pathway inhibitor, GLPG0634, significantly reduced the LPS-induced expression levels of BMP-2 and BMP-4.   Conclusion: Notch 2 may promote the calcification of cardiac VICs by modulating STAT expression.