Developing a sirtuin-1 activity assay to test novel sirt1 activators in a murine vascular smooth muscle cell model of Marfan syndrome
Embargo Date
2028-02-12
OA Version
Citation
Abstract
Marfan syndrome (MFS) is a disorder of the connective tissue characterized by a lack of fibrillin-1 (FBN1). Reduced levels of FBN1 leads to widespread impacts on the cardiovascular, ocular, and skeletal systems. One of the most dangerous clinical manifestations of MFS is reduced health of vascular smooth muscle, particularly of the aorta. This can lead to abnormal dilatations of the aorta, called aortic aneurysm, which can progress into life-threatening aortic dissections and ruptures. Sirtuin-1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase. SIRT1 has been shown to provide antioxidant and anti-inflammatory effects, to protect against the effects of aging and to mediate some of the benefits of calorie restriction. It was postulated that SIRT1 could become a potential therapeutic target against aortic aneurysms and possibly other vascular diseases. The goal of this thesis was twofold: (1) to optimize an enzyme-linked immunosorbent assay (ELISA) to test the effect of novel molecules on activating SIRT1 and (2) to develop a model of MFS in mouse vascular smooth muscle cells using silencing RNA to reduce FBN1, on which to test SRT1 activators.
Description
2025
License
Attribution 4.0 International