Zachary Rose
Research Mentor(s): Minerva Garcia-Barrio
Research Mentor School/College/Department: Internal Medicine
Presentation Date: 08/03/2022
Presentation Type: Poster
Poster Number: 14
Session: Session II: 1:30 – 2:20pm
Room: League Ballroom
Authors: Zachary Rose, Minerva Garcia-Barrio, PhD
Abstract
Vascular smooth muscle cells (VSMCs) possess the remarkable capacity to modulate their phenotype in response to external stimuli. Called phenotypic switching, this ability gives VSMCs many functions within the blood vessel. In healthy blood vessels, VSMCs exist primarily in the contractile phenotype to maintain vessel structure as well as to regulate blood flow. However, when the blood vessel is damaged or is growing, some VSMCs will switch to the synthetic phenotype in response to cytokines. Although necessary to the sustained health of blood vessels, the phenotypic switch can become problematic as blood vessels become exposed to excess oxidative stressors, such as in atherosclerosis, or physical injury, as in restenosis. Restenosis is a common complication of percutaneous coronary intervention (PCI), which is a treatment involving a “balloon” to open blocked arteries, usually accompanied with the application of a stent. In response to balloon injury, VSMCs mobilize in reaction to cytokines secreted by macrophages and will clonally expand to form neointima, a scar-like tissue. However, they are susceptible to overactive proliferation, often leading to restenosis. To mitigate restenosis after angioplasty, it is necessary to fully understand the mechanisms behind the phenotypic switch of VSMCs. The Wnt/beta-catenin signaling pathway has been well established to transduce cytokine signals in VSMCs, and studies in the lab of the principal investigator have revealed an interaction between this pathway and the Achaete Scute-like 3 (ASCL3) gene, which this lab also found to be a pro-migratory, pro-proliferative, anti-apoptotic factor. To further uncover the role of ASCL3 in VSMCs, we hypothesized that ASCL3 plays a direct role in cell division, whether as a transcription factor, chaperone for other transcription factors, and/or other structural roles. We found unexpected associations of the ASCL3 protein with cell division machinery and processes. Further dissecting these associations could establish ASCL3 as a novel target to prevent restenosis and other cardiovascular diseases with a proliferative component.
