Effects of age-dependent changes in cell size on endothelial cell proliferation and senescence through YAP1. Aging (Albany NY) 2019 Sep 05;11(17):7051-7069
Date
09/06/2019Pubmed ID
31487690Pubmed Central ID
PMC6756888DOI
10.18632/aging.102236Scopus ID
2-s2.0-85072345071 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
Angiogenesis - the growth of new blood capillaries- is impaired in aging animals. Biophysical factors such as changes in cell size control endothelial cell (EC) proliferation and differentiation. However, the effects of aging on EC size and the mechanism by which changes in cell size control age-dependent decline in EC proliferation are largely unknown. Here, we have demonstrated that aged ECs are larger than young ECs and that age-dependent increases in EC size control EC proliferation and senescence through CDC42-Yes-associated protein (YAP1) signaling. Reduction of aged EC size by culturing on single-cell sized fibronectin-coated smaller islands decreases CDC42 activity, stimulates YAP1 nuclear translocation and attenuates EC senescence. Stimulation of YAP1 or inhibition of CDC42 activity in aged ECs also restores blood vessel formation. Age-dependent changes in EC size and/or CDC42 and YAP1 activity may be the key control point of age-related decline in angiogenesis.
Author List
Mammoto T, Torisawa YS, Muyleart M, Hendee K, Anugwom C, Gutterman D, Mammoto AAuthors
Kathryn Hendee in the CTSI department at Medical College of Wisconsin - CTSIAkiko Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
Tadanori Mammoto MD, PhD Associate Professor in the Pediatrics department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
Adaptor Proteins, Signal TransducingAdult
Aging
Animals
Cell Cycle Proteins
Cell Size
Endothelial Cells
Female
Humans
Male
Mice, Inbred C57BL
Middle Aged
Neovascularization, Physiologic
Primary Cell Culture
Transcription Factors
cdc42 GTP-Binding Protein
