Microparticles Induce Cell Cycle Arrest Through Redox‐Sensitive Processes in Endothelial Cells: Implications in Vascular Senescence

Abstract

Chronic disease accelerates endothelial dysfunction in aging, a process associated with cell senescence. However, the mechanisms underlying this process are unclear. We examined whether endothelial cell (EC)‒derived microparticles (MPs) facilitate EC senescence and questioned the role of reactive oxygen species in this process. Senescence was induced by sequential passaging of primary mouse ECs. Cells retained phenotypic characteristics of ECs from passage 4 through passage 21. Passage 21 ECs exhibited features of senescence, including increased staining of senescence‐associated β‐galactosidase (SA‐βgal), a greater percentage of cells in G ₁ /G ₀ phase of the cell cycle, and increased phosphorylation of p66 ^Shc ( P P 2 ^●− (∼2.7‐fold) and H ₂ O ₂ (∼2.6‐fold), effects blocked by apocynin (nicotinamide adenine dinucleotide phosphate oxidase inhibitor) and rotenone (mitochondrial oxidase inhibitor) but not by allopurinol (xanthine oxidase inhibitor). MPs increased expression of cell cycle proteins p 21 cip1 and p16ink4a and stimulated phosphorylation of p66 ^Shc in ECs ( P J Am Heart Assoc . 2012;1:e001842 doi: 10.1161/JAHA.112.001842.)