Abstract
Abstract
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.