An Energy-Sensor Network Takes Center Stage During Endothelial Aging

Abstract

See related article, pages 1384–1393 Blood vessels form a critical interface between the environment and the organism by supplying nutrients, oxygen and macromolecules to all tissues and cells in the body. Endothelial cells (ECs) line the inner surface of the hierarchically branched blood vessel network and integrate functionally into different organs to support tissue growth and function in development, physiology, and disease. In healthy postnatal tissues, ECs are mostly quiescent and rarely migrate or proliferate. However, ECs possess a remarkable phenotypic plasticity in terms of being able to proliferate rapidly in response to vascular injury, tissue ischemia, or other stress conditions. This phenotypic plasticity progressively declines when ECs age and/or are permanently exposed to metabolic (eg, hyperglycemia) and environmental stressors (eg, oxidative stress) and coincides with the development of endothelial senescence.1 Cellular senescence is a stress response that is characterized by a robust inhibition of cell proliferation, which often becomes irreversible and independent of the initial stress signal.2 Senescence can be observed in most mammalian cells after extended propagation in culture and is related to the attrition of telomeres after repetitive cycles of cell divisions.2 In addition to telomere shortening, other stressors such as DNA damage, genomic instability, and oxidative stress can induce a similar growth arrest and trigger senescence.2 Senescent cells display characteristic alterations in cell morphology and gene expression that may weaken cellular functions. In ECs, these changes cause a phenotype that is proinflammatory, prothrombotic, and proatherosclerotic, which also negatively affects the vasodilatory, angiogenic, and regenerative properties of ECs and, thus, accelerates the development of several cardiovascular diseases.1 Despite advances in understanding the molecular mechanisms of endothelial senescence and vascular aging, the signaling networks governing the development and progression of EC senescence remain less well defined. In this issue of Circulation Research …