Endothelial cell senescence.

The wear and tear processes that are thought to contribute to human ageing may play an important role in the development of vascular diseases. One such process is cellular senescence. In endothelial cells the senescent phenotype can be induced by a number of factors, including telomere damage, oxidative stress and sustained mitogenic stimulation. Several lines of evidence indicate that endothelial cell senescence maybe relevant to vascular disease. In this chapter we examine the causes, mechanisms and regulation of endothelial cell senescence as they emerge from studies in cell culture. We also describe the senescent phenotype and discuss its pathophysiological implications. We review the evidence for the occurrence of endothelial cell senescence in vivo and examine findings in animal models of ageing and human genetic disorders that argue for and against a role of endothelial cell senescence in age-related vascular pathology. Finally, we address the particular case of endothelial progenitor cell senescence and discuss the relevance of this phenomenon for angiogenesis and vascular repair.