Phenotypic alterations in senescent large-vessel and microvascular endothelial cells

Endothelial cell senescence likely plays a key role in age-associated vascular diseases. A close relationship between in vitro and in vivo senescence of endothelial cells has been established. Therefore, elucidating the structural and functional changes occurring during long-term cultures of endothelial cells would contribute to clarifying the pathogenesis of vascular disorders in the elderly. We investigated the effects of replicative senescence on the architecture of bovine aortic vs microvascular endothelial cells. A marked increase in cell area was observed in both cell types, whereas dramatic morphological alterations were detected in microvascular endothelial cells only. The latter also showed age-associated reorganization of the actin cytoskeleton. Finally, both aortic and microvascular endothelial cells lost their migratory response to basic fibroblast growth factor with age. Our results highlight dramatic structural and functional alterations in senescent endothelial cells. Such rearrangements might account for in vivo endothelial cell alterations involved in age-associated vascular dysfunction.