Effects of Hypertension and Aging on Vascular Smooth Muscle Cell Contribution to Reconstituted Aortic Tissue Stiffness
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چکیده
EFFECTS OF HYPERTENSION AND AGING ON VASCULAR SMOOTH MUSCLE CELL CONTRIBUTION TO RECONSTITUTED AORTIC TISSUE STIFFNESS by Nancy Lisa Sehgel Aortic stiffness increases with hypertension and aging, and much of this increase has been thought to occur due to changes in the extracellular matrix. However, an increase in cell stiffness could also be important. To study the cellular contribution to aortic stiffness, a reconstituted aortic tissue model (composed of vascular smooth muscle cells (VSMCs) in a collagen matrix) was developed. VSMCs isolated from thoracic aortic samples of 5-week and 18-week old male spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats were passaged four times and then separately incubated in collagen for two days on a cylindrical mandrel. The resulting tissue rings were subjected to repeated 10% strain steps. The ratio of the steady-state increase of uniaxial stress following the step compared to the 10% strain determined tissue stiffness. This was measured for the intact reconstituted tissue; and following treatment with an actin cytoskeletal disrupter (cytochalasin D), which effectively removed the cellular contribution to stiffness. The cellular contribution was found from the difference between these stiffnesses. Aging and hypertension sharply increased VSMC stiffness (mean ± SEM): 18-week old SHR (1.45 ± 0.17 kPa) showed greater than a 6-fold difference compared to 5-week old SHR (0.24 ± 0.07 kPa), and greater than a 4-fold difference compared to 18week old WKY (0.33 ± 0.14 kPa). These data suggest that cellular contributions to aortic stiffness may increase with aging and hypertension. EFFECTS OF HYPERTENSION AND AGING ON VASCULAR SMOOTH MUSCLE CELL CONTRIBUTION TO RECONSTITUTED AORTIC TISSUE STIFFNESS by Nancy Lisa Sehgel A Thesis Submitted to the Faculty of New Jersey Institute of Technology in Partial Fulfillment of the Requirements for the Degree of Master of Science in Biomedical Engineering Department of Biomedical Engineering
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