Hartman Institute for Therapeutic Organ Regeneration

Laminar shear stress modulates endothelial luminal surface stiffness in a tissue-specific manner.

TitleLaminar shear stress modulates endothelial luminal surface stiffness in a tissue-specific manner.
Publication TypeJournal Article
Year of Publication2018
AuthorsMerna N, Wong AK, Barahona V, Llanos P, Kunar B, Palikuqi B, Ginsberg M, Rafii S, Rabbany SY
JournalMicrocirculation
Volume25
Issue5
Paginatione12455
Date Published2018 Jul
ISSN1549-8719
KeywordsAnimals, Arachidonic Acid, Biomechanical Phenomena, Cells, Cultured, Endothelial Cells, Lung, Mechanotransduction, Cellular, Mice, Microcirculation, Myocardium, Stress, Mechanical, Surface Properties
Abstract

<p><b>OBJECTIVE: </b>Endothelial cells form vascular beds in all organs and are exposed to a range of mechanical forces that regulate cellular phenotype. We sought to determine the role of endothelial luminal surface stiffness in tissue-specific mechanotransduction of laminar shear stress in microvascular mouse cells and the role of arachidonic acid in mediating this response.</p><p><b>METHODS: </b>Microvascular mouse endothelial cells were subjected to laminar shear stress at 4 dynes/cm for 12 hours in parallel plate flow chambers that enabled real-time optical microscopy and atomic force microscopy measurements of cell stiffness.</p><p><b>RESULTS: </b>Lung endothelial cells aligned parallel to flow, while cardiac endothelial cells did not. This rapid alignment was accompanied by increased cell stiffness. The addition of arachidonic acid to cardiac endothelial cells increased alignment and stiffness in response to shear stress. Inhibition of arachidonic acid in lung endothelial cells and embryonic stem cell-derived endothelial cells prevented cellular alignment and decreased cell stiffness.</p><p><b>CONCLUSIONS: </b>Our findings suggest that increased endothelial luminal surface stiffness in microvascular cells may facilitate mechanotransduction and alignment in response to laminar shear stress. Furthermore, the arachidonic acid pathway may mediate this tissue-specific process. An improved understanding of this response will aid in the treatment of organ-specific vascular disease.</p>

DOI10.1111/micc.12455
Alternate JournalMicrocirculation
PubMed ID29665185
PubMed Central IDPMC6407863
Grant ListR01 HL119872 / HL / NHLBI NIH HHS / United States
T32 HD060600 / HD / NICHD NIH HHS / United States

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