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Endocrine Abstracts (2016) 41 EP772 | DOI: 10.1530/endoabs.41.EP772

1National and Kapodistrian University of Athens, Medical School, Department of Biochemistry, Athens, Greece; 2National and Kapodistrian University of Athens, Medical School, First Department of Internal Medicine, Athens, Greece.


Introduction: Although the protective effects of 1,25(OH)2D3 on the early stages of atheromatosis process have been investigated, data on its influence on factors implicated in plaque vulnerability are limited. During these stages metalloproteinases MMP-2, MMP-9, their inhibitors TIMP-1,TIMP-2, the RANKL-RANK-OPG system and MCP-1 play a critical role. We aimed to investigate the effect of vitamin D on the expression of the above factors on endothelial cells. Methods: Human aortic endothelial cells (HAECs) were incubated with VitD for 24, 48,72 hours at a concentration range 10−8 – 10−11 in the absence of TNF-α or with VitD for 24 hours in the presence of TNF-α at concentration 10ng/ml for the last 6 hours. The mRNA expression of the aforementioned genes was assessed by real time-PCR. Zymography for MMP-2 and MMP-9 activity was also performed. OPG protein levels were also evaluated by western blot.

Results: VitD did not significantly change the expression of MMP-9, MMP-2, TIMP-1 and TIMP-2 at mRNA level at various incubation times and concentrations. The expression of OPG at mRNA was significantly increased in the presence of TNF-a and this effect became more pronounced when cells were preincubated with Vit D at concentration 10−9 M. Preincubation with p38 MAP kinase inhibitor totally abolished this result.

When cells activated with TNF-a, preincubation with Vit D resulted in a significant decrease in MMP-9 expression at 10−10 and 10−11M and increase in TIMP-2 expression while it didn’t affect the expression of MMP-2 and TIMP-1. Gelatin zymography revealed that Vit D decrease the active MMP-2 dose-dependently.

Conclusions: Vit D at physiologically achievable concentrations reduces the expression of MMP-9 and induces the expression of TIMP-2 at mRNA level implying a possible protective role in the later stages of atheromatosis, such as plaque vulnerability. Further studies are needed to elucidate the underlying mechanisms.

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