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Full-Text Articles in Engineering
Blood Flow Regulates Atherosclerosis Progression And Regression, Morgan A. Schake
Blood Flow Regulates Atherosclerosis Progression And Regression, Morgan A. Schake
Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research
Atherosclerosis is the most prevalent pathology of cardiovascular disease with no known cure. Despite the many systemic risk factors for atherosclerosis, plaques do not form randomly in the vasculature. Instead, they form around bifurcations and the inner curvature of highly curving arterial segments that contain so-called disturbed blood flow that is low in magnitude and multidirectional over the cardiac cycle. Conversely, straight, non-bifurcated arterial segments that contain moderate-to-high and unidirectional (i.e., normal) blood flow are protected from plaque development. Thus, blood flow is a key regulator of atherosclerosis that may be able to be leveraged to develop new therapeutics. Towards …
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
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 …
Temporally And Spatially Resolved Quantification Of Hemodynamic Forces And Endothelial Mechanics, Lori M. Lambert
Temporally And Spatially Resolved Quantification Of Hemodynamic Forces And Endothelial Mechanics, Lori M. Lambert
Department of Mechanical and Materials Engineering: Dissertations, Theses, and Student Research
The endothelium is a thin layer of endothelial cells that line the interior surface of an artery. Due to their direct contact with blood flow, endothelial cells experience varying hemodynamic forces and respond to these forces by altering their morphology. When plaque and other substances accumulate in the walls of arteries, i.e., atherosclerosis, endothelial cells have abnormal responses to blood flow. Studying atherosclerosis progression is, therefore, a two-fold investigation into 1) the hemodynamic forces that cause endothelial responses, and 2) the biological and mechanical responses of endothelial cells. The ultimate goal of this study was to develop an experimental …
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
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 …
Quantification Of Plaque Stiffness By Brillouin Microscopy In Experimental Thin Cap Fibroatheroma, Giuseppe Antonacci, Ryan M. Pedrigi, Avinash Kondiboyina, Vikram V. Mehta, Ranil De Silva, Carl Paterson, Rob Krams, Peter Torok
Quantification Of Plaque Stiffness By Brillouin Microscopy In Experimental Thin Cap Fibroatheroma, Giuseppe Antonacci, Ryan M. Pedrigi, Avinash Kondiboyina, Vikram V. Mehta, Ranil De Silva, Carl Paterson, Rob Krams, Peter Torok
Department of Mechanical and Materials Engineering: Faculty Publications
Plaques vulnerable to rupture are characterized by a thin and stiff fibrous cap overlaying a soft lipid-rich necrotic core. The ability to measure local plaque stiffness directly to quantify plaque stress and predict rupture potential would be very attractive, but no current technology does so. This study seeks to validate the use of Brillouin microscopy to measure the Brillouin frequency shift, which is related to stiffness, within vulnerable plaques. The left carotid artery of an ApoE-/- mouse was instrumented with a cuff that induced vulnerable plaque development in nine weeks. Adjacent histological sections from the instrumented and control arteries …
Systems Biology Of The Functional And Dysfunctional Endothelium, Jennifer Frueh, Nataly Maimari, Takayuki Homma, Sandra M. Bovens, Ryan M. Pedrigi, Leila Towhidi, Rob Krams
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 …