Sulodexide reduces senescence-related changes in human endothelial cells

BACKGROUND: Senescent endothelial cells acquire functional properties that make the vascular wall more prone to atherosclerotic changes. We tested whether senescence of the endothelial cells maintained in in vitro culture can be moderated by their simultaneous exposure to sulodexide. MATERIAL/METHODS: Replicative aging of the endothelial cells was studied during their 15 passages performed every 4 days in cells cultured in standard medium or in medium supplemented with sulodexide 0.5 LRU/mL. Changes in population doubling time and β-galactosidase activity were used as indexes of aging and compared with other cellular parameters. RESULTS: Repeated passages of endothelial cells induce their senescence, as reflected by prolongation of the population doubling time, increased β-galactosidase activity, oxidative stress and release of cytokines. Healing of the injured endothelial monolayer is impaired in senescent cells. Sulodexide partially prevents oxidative stress and totally eliminates other senescence-related changes such as increased release of MCP-1, lengthening of the population doubling time, and impaired healing of the cellular monolayer after its mechanical injury. CONCLUSIONS: Sulodexide prevented cellular senescence in cultured endothelial cells, moderating features of the cellular senescence in endothelial cells in in vitro conditions, which potentially may have practical application. The administration of sulodexide could potentially be used in prevention of atherosclerotic changes.