Hormones (Athens, Greece) · 2026
Effects of calcitriol (1,25(OH)₂D₃) on endothelial-derived factors implicated in atheromatous plaque vulnerability.
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Nasiri-Ansari Narjes, Rizou Aspasia, Flessa Christina-Maria, Randeva Manpal S, Spilioti Eliana, Chondrogianni Maria-Eleni, Dannenberg Lisa, Papavassiliou Athanasios G, Kassi Eva
Аннотация
BACKGROUND: Atherosclerosis progresses from endothelial dysfunction to arterial plaque vulnerability, rupture, erosion, and calcification. Vitamin D deficiency is an independent cardiovascular risk factor associated with advanced atherosclerotic disease. This study investigated whether calcitriol (1,25(OH)₂D₃), the active hormonal form of vitamin D, modulates the expression of MMP-2, MMP-9, TIMP-1, TIMP-2, MCP-1, RANK, RANKL, and OPG in human aortic endothelial cells (HAECs).
METHODS: Cells were treated with calcitriol alone or in combination with TNF-α. Gene expression was assessed by qPCR, MCP-1 and OPG protein levels were measured by ELISA, and MMP activity by zymography.
RESULTS: Calcitriol did not significantly affect basal MMP-2, MMP-9, TIMP-1, or TIMP-2 expression but reduced MCP-1 mRNA at 10⁻⁸ M. In TNF-α-activated cells, pre-incubation of cells with calcitriol decreased MMP-9 and MCP-1 expression, restored TIMP-2 levels, elevated the pro-/active-MMP-2 ratio and increased OPG mRNA expression, although this transcriptional effect was not accompanied by a corresponding increase in OPG protein levels.
CONCLUSION: The effects of calcitriol on human aortic endothelial cells suggest that calcitriol modulates inflammatory and extracellular matrix-remodeling markers in TNF-α-stimulated human aortic endothelial cells. Whether these changes contribute to plaque stability requires confirmation in more complex experimental models.
METHODS: Cells were treated with calcitriol alone or in combination with TNF-α. Gene expression was assessed by qPCR, MCP-1 and OPG protein levels were measured by ELISA, and MMP activity by zymography.
RESULTS: Calcitriol did not significantly affect basal MMP-2, MMP-9, TIMP-1, or TIMP-2 expression but reduced MCP-1 mRNA at 10⁻⁸ M. In TNF-α-activated cells, pre-incubation of cells with calcitriol decreased MMP-9 and MCP-1 expression, restored TIMP-2 levels, elevated the pro-/active-MMP-2 ratio and increased OPG mRNA expression, although this transcriptional effect was not accompanied by a corresponding increase in OPG protein levels.
CONCLUSION: The effects of calcitriol on human aortic endothelial cells suggest that calcitriol modulates inflammatory and extracellular matrix-remodeling markers in TNF-α-stimulated human aortic endothelial cells. Whether these changes contribute to plaque stability requires confirmation in more complex experimental models.