Vascular cell senescence in human atherosclerosis

摘要

Vascular cells have a finite lifespan when cultured in vitro and eventually enter an irreversible growth arrest called cellular senescence. Many of the changes in senescent vascular cell behavior are consistent with the changes seen in age-related vascular diseases.We have demonstrated the presence of senescent vascular cells in human atherosclerotic lesions, but not non-atherosclerotic lesions.Moreover, these cells express increased levels of proinflammatory molecules and decreased levels of endothelial nitric oxide synthase, suggesting that cellular senescence in vivo contributes to the pathogenesis of human atherosclerosis.One widely discussed hypothesis of senescence is the teleomere hypothesis. An increasing body of evidence has established the critical role of the telomere in vascular cell senescence. Another line of evidence suggests that telomere-independent mechanisms are also involved in vascular cell senescence. Activation of Ras, an important signaling molecule involved in atherogenic stimuli, induces vascular cell senescence and thereby promotes vascular inflammation in vitro and in vivo, while Akt negatively controls the lifespan of human vascular cells, both of which have been known to promote aging in organisms such as yeast and worms.These data suggest that the signaling pathways of longevity are conserved in human vascular cells. Further understanding of the mechanism underlying cellular senescence will provide insights into the potential of antisenescence therapy for vascular aging.