Vascular response to stress: protective action of the bisphosphonate alendronate

CAMPELO A.; CUTINI P.; MASSHEIMER V.

VASCULAR MEDICINE

SAGE PUBLICATIONS LTD

Lugar: London; Año: 2022 vol. 27 p. 425 - 432

1358-863X

Background: Since several extra bone actions of bisphosphonates have been proposed, in this work we studied the effect of the bisphosphonate alendronate (ALN) on the vascular response to extracellular environmental stress.Methods: Primary cultures of endothelial cells (EC) and vascular smooth muscle cells (VSMC) exposed to strained conditions were employed as experimental design. After ALN treatment, cell migration, proliferation, and angiogenesis assays were performed. The participation of signal transduction pathways in the biochemical action of ALN was also assessed. Results: In VSMC cultures, ALN counteracted the stimulation of cellular migration elicited by the proinflammatory agent lipopolysaccharide (LPS) or by high levels of calcium and phosphorus (osteogenic medium). Indeed, ALN reduced the increase of VSMC proliferation evoked by the stressors. When LPS and osteogenic medium were added simultaneously, the enhancement of cell proliferation dropped to control values in the presence of ALN. The mechanism of action of ALN involved the participation of nitric oxide synthase, MAPK and PKC signaling pathways. The study revealed that ALN exhibits a proangiogenic action. On EC, ALN enhanced vascular endothelial growth factor (VEGF) synthesis, and induced capillary-like tube formation in a VEGF dependent manner. The presence of vascular stress conditions (LPS or osteogenic medium) did not modify the proangiogenic action elicited by ALN. Conclusion: The findings presented suggest an extra-bone biological action of ALN, which could contribute to the maintenance of vascular homeostasis avoiding cellular damage elicited by environmental stress.