Hartman Institute for Therapeutic Organ Regeneration

Systems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch.

TitleSystems Biology Analysis of Temporal Dynamics That Govern Endothelial Response to Cyclic Stretch.
Publication TypeJournal Article
Year of Publication2022
AuthorsLai MW, Chow N, Checco A, Kunar B, Redmond D, Rafii S, Rabbany SY
JournalBiomolecules
Volume12
Issue12
Date Published2022 Dec 08
ISSN2218-273X
KeywordsCells, Cultured, Human Umbilical Vein Endothelial Cells, Humans, Mechanotransduction, Cellular, Stress, Mechanical, Systems Biology, Transcription Factors
Abstract

<p>Endothelial cells in vivo are subjected to a wide array of mechanical stimuli, such as cyclic stretch. Notably, a 10% stretch is associated with an atheroprotective endothelial phenotype, while a 20% stretch is associated with an atheroprone endothelial phenotype. Here, a systems biology-based approach is used to present a comprehensive overview of the functional responses and molecular regulatory networks that characterize the transition from an atheroprotective to an atheroprone phenotype in response to cyclic stretch. Using primary human umbilical vein endothelial cells (HUVECs), we determined the role of the equibiaxial cyclic stretch in vitro, with changes to the radius of the magnitudes of 10% and 20%, which are representative of physiological and pathological strain, respectively. Following the transcriptome analysis of next-generation sequencing data, we identified four key endothelial responses to pathological cyclic stretch: cell cycle regulation, inflammatory response, fatty acid metabolism, and mTOR signaling, driven by a regulatory network of eight transcription factors. Our study highlights the dynamic regulation of several key stretch-sensitive endothelial functions relevant to the induction of an atheroprone versus an atheroprotective phenotype and lays the foundation for further investigation into the mechanisms governing vascular pathology. This study has significant implications for the development of treatment modalities for vascular disease.</p>

DOI10.3390/biom12121837
Alternate JournalBiomolecules
PubMed ID36551265
PubMed Central IDPMC9775567
Grant ListR01 HL128158 / HL / NHLBI NIH HHS / United States

Weill Cornell Medicine
Hartman Institute for Therapeutic Organ Regeneration
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