3D Analysis of Arterial Injury to Study Nrf2 Dependent Inhibition of Neointimal Hyperplasia in Rats

Edward Bahnson, PhD presents the development and validation of a methodological approach using light-sheet fluorescence microscopy (LSFM) for the imaging of preclinical models of vascular injury with a focus of minimizing analysis bias while increasing precision and reproducibility.


Cardiovascular disease (CVD) is the leading cause of death and disability in the world. Severe, symptomatic atherosclerosis is treated by percutaneous or surgical revascularization, and the long-term success of both approaches is limited by arterial restenosis. Despite the advances in revascularization procedures, restenosis rates remain unacceptably high. Strategies to inhibit restenosis aim at reducing neointimal hyperplasia by inhibiting vascular smooth muscle cell (VSMC) proliferation and migration. Since increased production of reactive oxygen species promotes VSMC proliferation and migration, redox intervention to maintain vascular wall redox homeostasis holds the potential to inhibit arterial restenosis. A novel therapeutic approach is to restore the redox balance by activating nuclear factor erythroid 2-related factor 2 (Nrf2), the main antioxidant defense pathway present in our cells.


Standard methodology for the analysis of vascular injury has historically relied on 2D histology. Although this methodology has proven invaluable over the years, it is subject to shortcomings of 2D systems as well as significant user bias. In this webinar, Dr. Edward Bahnson discusses the development and validation of a methodological approach utilizing Light Sheet Fluorescence Microscopy (LSFM) for 3D imaging of preclinical vascular injury models. This approach minimizes analysis bias while increasing precision and reproducibility. He uses his studies on the mechanisms by which cinnamic aldehyde inhibits neointimal hyperplasia to demonstrate the application of this 3D approach to arterial injury analysis. He shows how LSFM allows us to see a full picture of the hyperplastic lesion, assess its topology, and assess both compensatory and constrictive remodeling. Additionally, he discusses its ability to multiplex, assess infiltration of immune cells, and analyze endothelial layer integrity.


Key learning objectives:
Local delivery of redox-based therapies can inhibit restenosis and have the potential to improve revascularization outcomes
3D analysis of arterial injury offers advantages over traditional 2D histology:
Unbiased determination of the region of injury and increased precision
Measurement of more parameters of arterial injury
Potential for discovery
Cinnamic aldehyde inhibits hyperplasia in a Nrf2-dependent manner