| dc.identifier.uri | http://hdl.handle.net/11401/76973 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | Vascular wall endothelial cells (ECs) are continuously subject to blood flow-induced shear stress and vasodilation-constriction induced tensile (or compressive) stress/strain. Altered mechanical environment can trigger EC activation and lead to atherosclerosis. Atherosclerosis is the main cause of coronary artery disease, which is the leading cause of death in the US. The functional and morphological response of ECs to fluid shear stress (FSS) or cyclic strain (CS) has been well documented. However, the responses of ECs to concomitant FSS and CS, have not been well characterized. A better understanding of this process can lead to more targeted preventive and therapeutic solutions for vascular diseases such as atherosclerosis. To investigate and better quantify the relationship between biomechanics and atherosclerosis formation, a patient-specific fluid-structure interaction (FSI) model of the left coronary artery was developed. The model incorporated transient blood flow, blood vessel cyclic bending and stretching, as well as myocardial contraction, to provide a physiologically relevant simulation of blood flow, shear stress and tensile strain conditions within the left coronary artery. Blood flow-induced FSS and CS on the vascular wall under various physiological and pathological conditions were estimated. In parallel, a novel shearing-stretching device was developed, to apply physiologically relevant FSS and CS concomitantly to cultured human coronary artery endothelial cells. Upon mechanical stimulation, endothelial cell morphological and functional responses were characterized. Changes in cell morphology were evaluated through cell area and elongation. Changes in EC functional responses were evaluated by characterizing EC activation, (i.e., ICAM-1 and phosphorylated PECAM-1 expression) and associated mechanotransduction (MAPK) pathway activation. Cells subjected to pathological FSS and CS mechanical conditions, in comparison to cells subjected to physiological conditions, were significantly bigger in area and presented significantly increased EC activation. Concomitant FSS and CS stimulation induced significant changes in endothelial cell function, compared to when cells were exposed to only FSS or CS alone. These findings demonstrate the complex interplay between altered FSS and CS, and suggest both FSS and CS need to be considered to investigate how mechanical stress/strain affects endothelial cell mechanotransduction, pathophysiological responses and disease initiation. | |
| dcterms.available | 2017-09-20T16:51:34Z | |
| dcterms.contributor | Yin, Wei | en_US |
| dcterms.contributor | Judex, Stefan | en_US |
| dcterms.contributor | Frame, Mary D. | en_US |
| dcterms.contributor | Colosqui, Carlos. | en_US |
| dcterms.creator | Sanchez, Daphne Meza | |
| dcterms.dateAccepted | 2017-09-20T16:51:34Z | |
| dcterms.dateSubmitted | 2017-09-20T16:51:34Z | |
| dcterms.description | Department of Biomedical Engineering | en_US |
| dcterms.extent | 151 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/76973 | |
| dcterms.issued | 2017-05-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:51:34Z (GMT). No. of bitstreams: 1
Sanchez_grad.sunysb_0771E_13333.pdf: 8427977 bytes, checksum: 6d4ad1a713034288e9a79b92e83f1b37 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | Biomedical engineering | |
| dcterms.subject | atherosclerosis, coronary artery, cyclic strain, endothelial cells, fluid-structure interaction, shear stress | |
| dcterms.title | THE EFFECT OF COMBINED FLUID SHEAR STRESS AND CYCLIC TENSILE STRETCH ON VASCULAR ENDOTHELIAL CELLS | |
| dcterms.type | Dissertation | |
