Effect of alendronate on cellular processes involved in atherosclerotic calcifications

CUTINI P, RAUSCHEMBERGER M, CAMPELO A, SANDOVAL M, MASSHEIMER V

Buenos Aires

Congreso; XXIX Annual Meeting of the Argentine Association of Osteology and Mineral Metabolism; 2012

Asociación Argentina de Osteología y Metabolismo Mineral

Bisphosphonates are effective treatments for osteoporosis and are supposed to inhibit vascular calcifications. Nitric oxide (NO) synthesis, smooth muscle cells (VSMC) migration and monocytes adhesion to endothelial cells (EC) are events involved in vascular calcifications. In this study we investigated whether alendronate (ALN) regulates these cellular through its direct action on vascular cells. To that end, we employed cultures of murine EC and VSMC treated with ALN. The effect of ALN was studied under basal or inflammation conditions induced by the presence of lipopolysacharide (LPS). EC treatment with ALN 5μM (15 min) significantly increased NO production (28.2±2.9 vs 46.3±6.0 nmol NO/mg protein, C vs ALN, pb0.01). Similar results were obtained with 10 and 50μM ALN (38 and 104% above control respectively). In VSMC, NO overproduction mainly through iNOS expression represents a deleterious fact that impairs vascular health. We found that 24 h of treatment with ALN (0.1-10μM) significantly inhibited VSMC NO production at all doses tested (54-37% below control respectively, pb0.01). In contrast, LPS markedly enhanced NO synthesis (104% above control, pb0.05). The presence of ALN prior to LPS treatment did not modify the stimulatory action of LPS. In migration assays we observed that ALN did not induce VSMC mobility compared with norepinephrine (migration inducer). ALN did not induce EC-monocytes adhesion while LPS did it(65%, pb0.01). When EC were treated with ALN 5 h prior to LPS addition, the effect of LPS was partially reversed. These results show that ALN modulates cellular events that mediate vascular calcifications.