Marlene Grenon, Jesus Aguado-Zunega, Michael S. Conte, Millie Hughes-Fulford
UCSF, San Francisco, CA.
OBJECTIVES: Mechanical forces including gravity affect mechanotransduction and cell function. The goal of this study was to investigate the impact of mechanical unloading (MU) and loading (ML) of endothelial cells (ECs) with microgravity and hypergravity respectively, with the hypothesis that MU alters expression of inflammatory and adhesion molecule gene expression and these changes are reversed by ML.
METHODS: Human umbilical vascular ECs grown to confluency were studied. A desktop random positioning machine and a gravitational cell-loading apparatus provided MU and ML. The experimental conditions included: 1) controls exposed to 1-gravity environment for 24 h (CL), 2) MU for 24 hours, and 3) MU for 24 hours with three 30-minute periods of ML of 12-gravity (MU/ML). Gene expression was studied with reverse transcription followed by real-time quantitative polymerase chain reaction (qRTPCR).
RESULTS: MU led to a significant decrease in gene expression of the adhesion molecules ICAM-1, VCAM-1, E-Selectin, as well as TNF-α, IL-6 and VEGF. In contrast, NOS-3, Caveolin-1 and -2 were significantly increased with MU. The changes observed in gene expression with MU were reversed by gravitational mechanical loading (MU/ML).
CONCLUSIONS: Gravitational MU decreases inflammatory and adhesion molecule gene expression and these changes are reversed by short periods of ML. This points towards the importance of gravitational loading in ECs function and cellular interactions.
AUTHOR DISCLOSURES: J. Aguado-Zunega, Nothing to disclose; M. S. Conte, Nothing to disclose; M. Grenon, Nothing to disclose; M. Hughes-Fulford, Nothing to disclose.
Posted April 2012