Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress
Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2007
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| Online Access: | http://hdl.handle.net/1721.1/36167 |
| _version_ | 1826200800856113152 |
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| author | Morss, Alisa Sharon |
| author2 | Elazer R. Edelman. |
| author_facet | Elazer R. Edelman. Morss, Alisa Sharon |
| author_sort | Morss, Alisa Sharon |
| collection | MIT |
| description | Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006. |
| first_indexed | 2024-09-23T11:41:59Z |
| format | Thesis |
| id | mit-1721.1/36167 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T11:41:59Z |
| publishDate | 2007 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/361672019-04-11T13:34:36Z Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress Morss, Alisa Sharon Elazer R. Edelman. Harvard University--MIT Division of Health Sciences and Technology. Harvard University--MIT Division of Health Sciences and Technology. Harvard University--MIT Division of Health Sciences and Technology. Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2006. Includes bibliographical references. Endothelial cells and basement membrane interact as a biochemical and mechanical co-regulatory unit. The wide spectrum of manifestations of diabetic vascular disease could be related to altered kinetics of vasoactive compounds within this regulatory unit. We hypothesized that hyperglycemic stress mediates storage, release, and function of fibroblast growth factor-2 (FGF-2) through changes in interaction between endothelial cells and basement membrane. We discovered that basement membrane associated FGF-2 increased linearly with culture glucose concentration. Using novel assays, we demonstrated that FGF-2 binding kinetics were surprisingly unchanged over a range of basement membrane culture glucose. Instead, the combination of increased endothelial cell apoptosis-associated FGF-2 release and enhanced endothelial cell permeability allowed more FGF-2 to bind into the basement membrane. Such high levels of basement membrane FGF-2 abrogated the effects of hyperglycemia on proliferation but not apoptosis. An FGF-2 stimulus returned endothelial cell proliferation close to euglycemic levels, but increased apoptosis was still evident as FGF-2 signaling down an intracellular survival pathway was inhibited by glucose. (cont.) These same findings were confirmed in vivo where FGF-2 levels were elevated in the aortic subendothelial space of diabetic animals. This thesis suggests a new paradigm for active cellular control of basement membrane and indicates the complexities of growth factor signaling in endothelial cells. Characterization of the interaction between endothelial cells and basement membrane in health and disease may advance our understanding of diabetic vascular disease and lead to development of novel biomimetic materials for therapeutic intervention. by Alisa Sharon Morss. Ph.D. 2007-02-21T11:50:29Z 2007-02-21T11:50:29Z 2006 2006 Thesis http://hdl.handle.net/1721.1/36167 73726716 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 182 leaves application/pdf Massachusetts Institute of Technology |
| spellingShingle | Harvard University--MIT Division of Health Sciences and Technology. Morss, Alisa Sharon Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress |
| title | Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress |
| title_full | Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress |
| title_fullStr | Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress |
| title_full_unstemmed | Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress |
| title_short | Endothelial cells and basement membrane : a co-regulatory unit for fibroblast growth factor-2 in hyperglycemic stress |
| title_sort | endothelial cells and basement membrane a co regulatory unit for fibroblast growth factor 2 in hyperglycemic stress |
| topic | Harvard University--MIT Division of Health Sciences and Technology. |
| url | http://hdl.handle.net/1721.1/36167 |
| work_keys_str_mv | AT morssalisasharon endothelialcellsandbasementmembraneacoregulatoryunitforfibroblastgrowthfactor2inhyperglycemicstress |