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dc.contributor.authorArevalos, C. Alexander
Walborn, Amanda T.
Rupert, Amanda A.
Berg, Jonathan M.
Godfrey, Elizabeth L.
Nguyen, Jacqueline M.V.
Grande-Allen, K. Jane
dc.date.accessioned 2017-06-15T15:30:09Z
dc.date.available 2017-06-15T15:30:09Z
dc.date.issued 2015
dc.identifier.citation Arevalos, C. Alexander, Walborn, Amanda T., Rupert, Amanda A., et al.. "Regulation of valve endothelial cell vasculogenic network architectures with ROCK and Rac inhibitors." Microvascular Research, 98, (2015) Elsevier: 108-118. https://doi.org/10.1016/j.mvr.2015.01.008.
dc.identifier.urihttps://hdl.handle.net/1911/94868
dc.description.abstract Objective: The age- and disease-dependent presence of microvessels within heart valves is an understudied characteristic of these tissues. Neovascularization involves endothelial cell (EC) migration and cytoskeletal reorientation, which are heavily regulated by the Rho family of GTPases. Given that valve ECs demonstrate unique mesenchymal transdifferentiation and cytoskeletal mechanoresponsiveness, compared to vascular ECs, this study quantified the effect of inhibiting two members of the Rho family on vasculogenic network formation by valve ECs. Approach and results: A tubule-like structure vasculogenesis assay (assessing lacunarity, junction density, and vessel density) was performed with porcine aortic valve ECs treated with small molecule inhibitors of Rho-associated serine-threonine protein kinase (ROCK), Y-27632, or the Rac1 inhibitor, NSC-23766. Actin coordination, cell number, and cell migration were assessed through immunocytochemistry, MTT assay, and scratch wound healing assay. ROCK inhibition reduced network lacunarity and interrupted proper cell–cell adhesion and actin coordination. Rac1 inhibition increased lacunarity and delayed actin-mediated network formation. ROCK inhibition alone significantly inhibited migration, whereas both ROCK and Rac1 inhibition significantly reduced cell number over time compared to controls. Compared to a vascular EC line, the valve ECs generated a network with larger total vessel length, but a less smooth appearance. Conclusions: Both ROCK and Rac1 inhibition interfered with key processes in vascular network formation by valve ECs. This is the first report of manipulation of valve EC vasculogenic organization in response to small molecule inhibitors. Further study is warranted to comprehend this facet of valvular cell biology and pathology and how it differs from vascular biology.
dc.language.iso eng
dc.publisher Elsevier
dc.rights This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by Elsevier.
dc.title Regulation of valve endothelial cell vasculogenic network architectures with ROCK and Rac inhibitors
dc.type Journal article
dc.citation.journalTitle Microvascular Research
dc.subject.keywordAortic valve
Rac1
Rho kinase
Valve endothelial cell
Vasculogenesis
dc.citation.volumeNumber 98
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1016/j.mvr.2015.01.008
dc.identifier.pmcid PMC4974942
dc.identifier.pmid 25660064
dc.type.publication post-print
dc.citation.firstpage 108
dc.citation.lastpage 118


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