Year Two: siRNA-Based Gene Silencing in the Extracellular Matrix of Abdominal Aortic Aneurysms with Simulation Modeling

Overview

Abdominal aortic aneurysms (AAAs) are expansions of the aorta characterized by enzymatic breakdown of wall elastic fiber structures, causing weakening & fatal rupture. Current management involves periodic image-based growth monitoring with no established drug-based therapies, and reversing disease pathophysiology is difficult as cells are unable to regenerate new elastic fibers. Year one of experimentation served as a proof of concept to verify the feasibility of this technique and the use of siRNA to stimulate elastic matrix assembly. This year's research expands to investigate 16 genes, with the objective to determine the impacts of EGFR silencing in aneurysmal aortic smooth muscle cells (EaRASMC), and observe potential unintended consequences of the technique, with a goal to stimulate the regeneration of elastic matrix and inhibit proteolytic enzymes. It was hypothesized that siRNA sequences that inhibit the EGFR gene can therapeutically reverse matrix aberrations associated with AAAs to regenerate & restore healthy elastic matrix and slow/reverse AAA growth. siRNA effects on MMP expression levels & elastic fiber assembly were studied in in vitro cultures of EaRASMC from simulated rat models. Relative gene expression was determined with qPCR. Improved elastic matrix regeneration was achieved through decreases in MMPS & increases in elastic matrix production. This research demonstrates how siRNA-based gene silencing to augment elastogenesis may be used as a treatment for AAAs.

Competition history

• JSHS 2023 Category not listed

Resources

• National JSHS abstract book ↗

Related projects

Closest projects by meaning, across every fair and year in the corpus.