Nanoscience and Nanotechnology 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 …

Influence Of Shear Stress Magnitude And Direction On Atherosclerotic Plaque Composition, Ryan M. Pedrigi, Vikram V. Mehta, Sandra M. Bovens, Zahra Mohri, Christian Bo Poulsen, Willy Gsell, Jordi L. Tremoleda, Leila Towhidi, Ranil De Silva, Enrico Petretto, Rob Krams

Department of Mechanical and Materials Engineering: Faculty Publications

The precise flow characteristics that promote different atherosclerotic plaque types remain unclear. We previously developed a blood flow-modifying cuff for ApoE^−/− mice that induces the development of advanced plaques with vulnerable and stable features upstream and downstream of the cuff, respectively. Herein, we sought to test the hypothesis that changes in flow magnitude promote formation of the upstream (vulnerable) plaque, whereas altered flow direction is important for development of the downstream (stable) plaque. We instrumented ApoE^−/− mice (n=7) with a cuff around the left carotid artery and imaged them with micro-CT (39.6 μm resolution) eight to nine weeks …

Inducing Persistent Flow Disturbances Accelerates Atherogenesis And Promotes Thin Cap Fibroatheroma Development In D374y-Pcsk9 Hypercholesterolemic Minipigs, Ryan M. Pedrigi, Christian Bo Poulsen, Vikram V. Mehta, Niels Ramsing Holm, Nilesh Pareek, Anouk L. Post, Ismail Dogu Kilic, Winston A.S. Banya, Gianni Dall'ara, Alessio Mattesini, Martin M. Bjorklund, Niels P. Andersen, Anna K. Grondal, Enrico Petretto, Nicolas Foin, Justin E. Davies, Carlo Di Mario, Jacob Fog Bentzon, Hans Erik Botker, Erling Falk, Rob Krams, Ranil De Silva

Department of Mechanical and Materials Engineering: Faculty Publications

Background—Although disturbed flow is thought to play a central role in the development of advanced coronary atherosclerotic plaques, no causal relationship has been established. We evaluated whether inducing disturbed flow would cause the development of advanced coronary plaques, including thin cap fibroatheroma (TCFA).

Methods and Results—D374Y-PCSK9 hypercholesterolemic minipigs (N=5) were instrumented with an intracoronary shear-modifying stent (SMS). Frequency-domain optical coherence tomography was obtained at baseline, immediately post-stent, 19, and 34 weeks and used to compute shear stress metrics of disturbed flow. At 34 weeks, plaque type was assessed within serially-collected histological sections and co-registered to …