title: Static mechanical strain induces capillary endothelial cell cycle re-entry and sprouting.
abstract: Vascular endothelial cells are known to respond to a range of biochemical and time-varying mechanical cues that can promote blood vessel sprouting termed angiogenesis. It is less understood how these cells respond to sustained (i.e., static) mechanical cues such as the deformation generated by other contractile vascular cells, cues which can change with age and disease state. Here we demonstrate that static tensile strain of 10%, consistent with that exerted by contractile microvascular pericytes, can directly and rapidly induce cell cycle re-entry in growth-arrested microvascular endothelial cell monolayers. S-phase entry in response to this strain correlates with absence of nuclear p27, a cyclin-dependent kinase inhibitor. Furthermore, this modest strain promotes sprouting of endothelial cells, suggesting a novel mechanical 'angiogenic switch'. These findings suggest that static tensile strain can directly stimulate pathological angiogenesis, implying that pericyte absence or death is not necessarily required of endothelial cell re-activation.
authors.affiliation: Department of Materials Science & Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139. BioSystems & Micromechanics Interdisciplinary Research Group (BioSyM), Singapore-MIT Alliance in Research & Technology (SMART), Singapore 138602.
authors.forename: A S
authors.initials: AS
authors.lastname: Zeiger
authors.forename: F D
authors.initials: FD
authors.lastname: Liu
authors.forename: J T
authors.initials: JT
authors.lastname: Durham
authors.forename: A
authors.initials: A
authors.lastname: Jagielska
authors.forename: R
authors.initials: R
authors.lastname: Mahmoodian
authors.forename: K J
authors.initials: KJ
authors.lastname: Van Vliet
authors.forename: I M
authors.initials: IM
authors.lastname: Herman
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002453:Cell Cycle; D042783:Endothelial Cells / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic; D020286:Pericytes / Q000502:physiology*; D013314:Stress, Mechanical; D013718:Tensile Strength