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dc.contributor.authorBuchanan, Jenna
dc.date.accessioned2016-03-23T23:34:38Zen
dc.date.available2016-03-23T23:34:38Zen
dc.date.issued2016-03-23
dc.identifier.urihttp://hdl.handle.net/10150/603563
dc.descriptionA Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.en
dc.description.abstractBackground: Studies have shown that Alzheimer’s Disease (AD) is strongly associated with the presence of atherosclerosis risk factors, including hyperlipidemia (and associated increased free fatty acids), hypertension and diabetes. We tested the hypotheses that β‐ amyloid proteins (Aβ) or palmitic acid (PA), a saturated fatty acid and known atherosclerotic risk factor, cause impaired function and viability of human umbilical vein endothelial cells (HUVEC), and that together, they exert synergistic effects on HUVEC dysfunction. Methods: HUVEC were exposed for 18‐20 hours to vehicle, Aβ42 (2μM) ± PA (150μM) or PA (150μM) while some HUVEC were exposed to a 4‐hour pre‐treatment with PA (150mM) followed wash and treatment with vehicle ± Aβ42 (2μM) for 18‐20 hours. Outcomes measured included: (1) nitric oxide (NO) and measures of oxidative stress (superoxide) and nitrosative stress (peroxynitrite), (2) inflammatory and associated markers (interleukins (IL)‐6, IL‐8, Reaction for Advanced Glyocolytic End Products (RAGE) 1 and 2, and Matrix Metalloproteinases (MMP‐9) by PCR. Results: HUVECs exposed to either Aβ or PA showed impaired NO production and increased superoxide and peroxynitrite when compared to vehicle control. Co‐treatment with Aβ and PA did not cause a statistically significant change compared to Aβ or PA alone. HUVEC demonstrated variable inflammatory responses following exposure to either Aβ or PA. Treatment with PA resulted in upregulation of RAGE2 gene expression (p<0.003) and trend towards IL‐6 overexpression (p=0.059). Co‐treatment with both Aβ and PA led to an observed increase in inflammatory responses versus control, but the results did not reach statistical significance. Conclusion: Independent exposure of HUVECs to Aβ and PA caused decreased nitric oxide production and increased oxidative and nitrosative stress. HUVECs did not demonstrate Aβ‐ induced endothelial cell inflammation. Co‐treatment with 2μM Aβ and PA 150μM did not result in a synergistic or additive increase in endothelial cell inflammatory responses.
dc.description.sponsorshipThe National Institutes of Health (NIA R21AG044723) and the VA ORD (MeritI01BX007080)en
dc.language.isoen_USen
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.subject.meshVascular Diseasesen
dc.subject.meshFatty Acidsen
dc.subject.meshAmyloiden
dc.subject.meshAlzheimer Diseaseen
dc.titleA Study of the Vascular Basis of Alzheimer’s Disease: The Role of Beta Amyloid (Aβ) Proteins and Saturated Fatty Acids in Endothelial Dysfunction and Inflammationen_US
dc.typetext; Electronic Thesisen
dc.contributor.departmentThe University of Arizona College of Medicine - Phoenixen
dc.description.collectioninformationThis item is part of the College of Medicine - Phoenix Scholarly Projects 2016 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.en_US
dc.contributor.mentorMigrino, Raymond Q.en
html.description.abstractBackground: Studies have shown that Alzheimer’s Disease (AD) is strongly associated with the presence of atherosclerosis risk factors, including hyperlipidemia (and associated increased free fatty acids), hypertension and diabetes. We tested the hypotheses that β‐ amyloid proteins (Aβ) or palmitic acid (PA), a saturated fatty acid and known atherosclerotic risk factor, cause impaired function and viability of human umbilical vein endothelial cells (HUVEC), and that together, they exert synergistic effects on HUVEC dysfunction. Methods: HUVEC were exposed for 18‐20 hours to vehicle, Aβ42 (2μM) ± PA (150μM) or PA (150μM) while some HUVEC were exposed to a 4‐hour pre‐treatment with PA (150mM) followed wash and treatment with vehicle ± Aβ42 (2μM) for 18‐20 hours. Outcomes measured included: (1) nitric oxide (NO) and measures of oxidative stress (superoxide) and nitrosative stress (peroxynitrite), (2) inflammatory and associated markers (interleukins (IL)‐6, IL‐8, Reaction for Advanced Glyocolytic End Products (RAGE) 1 and 2, and Matrix Metalloproteinases (MMP‐9) by PCR. Results: HUVECs exposed to either Aβ or PA showed impaired NO production and increased superoxide and peroxynitrite when compared to vehicle control. Co‐treatment with Aβ and PA did not cause a statistically significant change compared to Aβ or PA alone. HUVEC demonstrated variable inflammatory responses following exposure to either Aβ or PA. Treatment with PA resulted in upregulation of RAGE2 gene expression (p<0.003) and trend towards IL‐6 overexpression (p=0.059). Co‐treatment with both Aβ and PA led to an observed increase in inflammatory responses versus control, but the results did not reach statistical significance. Conclusion: Independent exposure of HUVECs to Aβ and PA caused decreased nitric oxide production and increased oxidative and nitrosative stress. HUVECs did not demonstrate Aβ‐ induced endothelial cell inflammation. Co‐treatment with 2μM Aβ and PA 150μM did not result in a synergistic or additive increase in endothelial cell inflammatory responses.


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