Engineering Science and Materials Commons^™

Disturbed Cyclical Stretch Of Endothelial Cells Promotes Nuclear Expression Of The Pro-Atherogenic Transcription Factor Nf-Kb, Ryan M. Pedrigi, Konstantinos I. Papadimitriou, Avinash Kondiboyina, Sukhjinder Sidhu, James Chau, Miten B. Patel, Daniel C. Baeriswyl, Emmanuel M. Drakakis, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

Exposure of endothelial cells to low and multidirectional blood flow is known to promote a pro-atherogenic phenotype. The mechanics of the vessel wall is another important mechano-stimulus within the endothelial cell environment, but no study has examined whether changes in the magnitude and direction of cell stretch can be pro-atherogenic. Herein, we developed a custom cell stretching device to replicate the in vivo stretch environment of the endothelial cell and examined whether low and multidirectional stretch promote nuclear translocation of NF-kB. A fluid–structure interaction model of the device demonstrated a nearly uniform strain within the region of cell attachment and …

Integration Of Flow Studies For Robust Selection Of Mechanoresponsive Genes, Nataly Maimari, Ryan M. Pedrigi, Alessandra Russo, Krysia Broda, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

Blood flow is an essential contributor to plaque growth, composition and initiation. It is sensed by endothelial cells, which react to blood flow by expressing >1000 genes. The sheer number of genes implies that one needs genomic techniques to unravel their response in disease. Individual genomic studies have been performed but lack sufficient power to identify subtle changes in gene expression. In this study, we investigated whether a systematic meta-analysis of available microarray studies can improve their consistency.

We identified 17 studies using microarrays, of which 6 were performed in vivo and 11 in vitro. The in vivo studies were …

Systems Biology Of The Functional And Dysfunctional Endothelium, Jennifer Frueh, Nataly Maimari, Takayuki Homma, Sandra M. Bovens, Ryan M. Pedrigi, Leila Towhidi, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

This review provides an overview of the effect of blood flow on endothelial cell (EC) signalling pathways, applying microarray technologies to cultured cells, and in vivo studies of normal and atherosclerotic animals. It is found that in cultured ECs, 5–10% of genes are up- or down-regulated in response to fluid flow, whereas only 3–6% of genes are regulated by varying levels of fluid flow. Of all genes, 90%are regulated by the steady part of fluid flow and 10% by pulsatile components. The associated gene profiles show high variability from experiment to experiment depending on experimental conditions, and importantly, the bioinformatical …