Date of Graduation

5-2016

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Biological Sciences

Advisor

Balachandran, Kartik

Reader

McNabb, David

Second Reader

Lewis, Jeffrey

Third Reader

Kumar, T. K. S.

Abstract

Calcific Aortic Valve Disease is responsible for approximately 28,000 deaths annually and the complete mechanism is not completely understood. The disease is known to be effected by an inflammatory response, osteogenic response and an oxidative stress response that leads to thickening and mineralization of the aortic valve. Originally, this disease was thought to be brought on by age and deterioration of the valve but these rapid stress responses when the valve is disrupted by biochemical and mechanical stress has led to its classification as an active disease. Smoking has been shown to have many of the same effects experienced by CAVD but whether the two are directly connected as not been determined. The focus of this Honors project is thus to identify if smoking will elicit a pathological response in vitro to better understand the pathways induced and to identify ways to mitigate smoking-related valve disease. It is hypothesized that cigarette smoke will lead to an inflammatory response, osteogenic-like response, and oxidative stress by analyzing the changes in TGF-B1, IL-6, osteopontin, osteocalcin, RUNX2, and LOX-1. To achieve this, VICs were subjected to 1% and 0.5% Marlboro Red and Silver cigarettes for 6, 24, and 48 hours and were analyzed via RT-PCR and Western Blot. This study concluded that smoking results in the upregulation of IL6 when examined with RT- PCR and the presence of LOX-1 when examined by Western Blot. The presence of these two factors proves that there was an increase of oxidized LDLs as is characteristic of oxidative stress. These results, in combination with the fact that osteopontin, osteocalcin, and RUNX2 gene expression were upregulated at the 6 hour and 48- hour time points, also suggest that there is still a possibility that smoking could induce an osteogenic response if the VICs were subjected to the smoking extracts for longer time periods. The degree to which smoking induces an inflammatory response and an osteogenic response will have to be further tested.

Keywords

calcific aortic valve disease, cardiovascular disease, tobacco use

Available for download on Monday, May 06, 2019

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