Date on Master's Thesis/Doctoral Dissertation
JB Speed School of Engineering
Committee Co-Chair (if applicable)
radiation exposure; extracellular matrix
Ionizing radiation has been associated with various cardiovascular complications; however, the associated molecular changes from radiation exposure still remain largely uncharacterized. Alterations to the cardiovascular tissue microenvironment, i.e. the extracellular matrix (ECM), directly affect the function of integrated vascular cells, including cell adhesion, potential to form vessels, and endothelial permeability, which can promote cardiovascular pathologies. The ECM is constantly remodeled in response to stimuli, such as TGF-β1, which leads to excessive ECM accumulation. We hypothesize that radiation exposure will alter the cardiovascular ECM. Human Cardiac Fibroblasts (HCFs) were utilized to produce ECM as an in vitro model to study changes in cardiovascular ECM from exposure to 0 and 1 Gy of γ-radiation. We verified that the ECM produced by these cells over 7 days of culture contained collagen and fibronectin. HCFs were radiosensitive to 1 Gy of radiation, as the irradiated cells exhibited γ-H2AX foci. Intracellular reactive oxygen species (ROS), a known activator of latent TGF-β1, was increased in HCF immediately after radiation. In addition, irradiated HCF contained SMAD 2/3 in their nuclei and expressed α-smooth muscle actin, which are indicative of TGF-β1 activation. Measurement of total ECM protein and morphology demonstrated an increase in ECM protein production and an altered ECM structure from HCF exposed to 1 Gy radiation compared to sham control. In conclusion, we demonstrate that ionizing radiation induces structural and molecular changes in cardiovascular ECM. Our data vi further indicates that γ-irradiation activates TGF-β1 downstream signaling cascades, which may be a primary contributor of ECM remodeling in vascular tissue. Future studies relating ECM remodeling and cardiovascular cell function may help improve our understanding of cardiovascular risks from radiation exposure.
Allen, Nicholas, "Gamma-radiation exposure alters the cardiovascular extracellular matrix." (2016). Electronic Theses and Dissertations. Paper 2483.