Understanding the role of the transcription factor Bcl11b in vascular smooth muscle cell proliferation and aortic aneurysm development

Date
2022
DOI
Authors
Kunze, Abigail Lauren
Version
OA Version
Citation
Abstract
BACKGROUND: Aortic aneurysms are potentially fatal vascular conditions, with no non-surgical treatments currently approved (Kuivaniemi et al., 2014). Recently, the Seta laboratory discovered that the transcription factor, Bcl11b, is present in the vascular smooth muscle cells that comprise the aorta and has been linked to arterial stiffness. To further investigate the role of Bcl11b in vascular function, a vascular smooth muscle cell-specific Bcl11b knockout (BSMKO) was created and challenged with Angiotensin II (Ang-II), a hypertensive stimulus. Interestingly, it was found that BSMKO mice developed aortic aneurysms while their control littermates did not. This experiment led to the hypothesis that Bcl11b may play a role in the development of aortic aneurysms. METHODS: Using Ingenuity Pathway Analysis (IPA) we compared RNA-sequencing data generated from aortas isolated from wild-type (WT) and BSMKO after Ang-II-treatment and identified differentially expressed genes important in the cell cycle pathway. To test the hypothesis that Bcl11b regulates the VSMC cell cycle, we performed two assays; a propidium iodide uptake and a 5-ethynyl-2′-deoxyuridine (EdU) Incorporation Assay which were both quantified using flow cytometry. An in vitro model was used where VSMCs isolated from WT and BSMKO mice were treated with growth stimulant PDGF. EdU incorporation was also performed in vivo in WT and BSMKO mice treated with Ang-II. RESULTS: Our results indicate that there was a significant increase in the percent of cells in the S phase when stimulated with PDGF in the WT mice, but not in the BSMKO mice in the in vitro model. The in vivo model did not indicate statistically significant differences between Ang-II-treated WT and BSMKO mice. These results suggest that VSMCs lacking Bcl11b are less proliferative than WT VSMCs when stimulated with PDGF.
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