SERMs, biphosphonate and vascular function

RAUSCHEMBERGER M.B.; CUTINI P.; CEPEDA S.; SANDOVAL M.; MASSHEIMER V.

Ciudad Autónoma de Buenos Aires

Congreso; XXX Reunión Anual de la Asociación Argentina de Osteología y Metabolismo Mineral (AAOMM); 2013

Vascular calcification (VCa) represents an advanced stage of atherosclerotic lesion. At vascular level, Raloxifene (Ral), and Alendronate (Al) exhibit regulatory actions through different mechanisms. The aim of the present work was to compare the effect of these drugs on cellular events involved in CaV. Effects of in vitro treatments with 10 nM Ral or 5 μM AL on: a) NO production by either endothelial cells (EC) or vascular smooth muscular cells (VSMC), b) monocyte?platelet?endothelium interaction c) VSMC migration was studied under physiological or calcification conditions (1 or 5 mM extracellular Ca concentration respectively). In CE, both drugs markedly stimulated NO production (85 ± 2; 142.8 ± 1.3; 132 ± 7 nmol NO/mg prot, C, Ral, Al, p < 0.01). In endothelium-blood cells, interaction studies, 24 h of treatment with Al prevented monocyte adhesion to EC induced by LPS (20 ± 3; 42 ± 8; 28 ± 6 monocytes/field, C, LPS, LPS + AL). Indeed, Ral significantly inhibited endothelial platelet aggregation (79?55% inhibition, 1?10 nM Ral, p < 0.05). In VSMC both drugs inhibited NO production (144 ± 9; 29 ± 2.3; 66.2 ± 3 nmol NO/mg prot C, Ral, Al, p < 0.05). Cells migration assays determined that 48?72 h of drug treatment prevent VSMC motility. Under CaV conditions (5 mM Ca), the effect of Al on the NO synthesis either on EC or VSMC was sustained (160% stimulus above control in EC; 48% of inhibition respect to control values in VSMC, p < 0.02). The calcium channel antagonist nifedipine did not modify the bisphosphonate action. However, in CaV conditions, Ral loses its ability to regulate NO synthesis in both cell types. These results suggest that, although both drugs exert a positive effect on vascular homeostasis under physiological conditions, in an unfavorable environment Ral vascular actions were impaired meanwhile Al effects were sustained.