ORCID Profile
0000-0001-8578-0517
Current Organisation
University of North Carolina at Chapel Hill
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Publisher: American Association for the Advancement of Science (AAAS)
Date: 31-10-2023
Publisher: Cold Spring Harbor Laboratory
Date: 23-12-2022
DOI: 10.1101/2022.12.23.521811
Abstract: Cardiovascular disease (CVD) remains the leading cause of mortality worldwide. Preclinical studies to research and validate therapeutic interventions for CVD often depend on two-dimensional histological surveys. The use of light sheet fluorescent microscopy together with optical clearing methods amenable to immunofluorescent staining are recent advances, all of which deliver detailed three-dimensional rendering of vessels. This offers the ability to describe and quantify features critical in CVD models, specifically, atherosclerotic plaque burden in atherosclerotic animal models. The main challenge for this approach remains the lengthy, hands-on, analysis time. Labkit is a user-friendly Fiji plugin that applies a machine-learning algorithm to create three-dimensional renderings from large microscopy data. The application of this plugin is expected to decrease the hands-on analysis time required to generate accurate volumetric renderings of atherosclerotic plaque burden in athero-prone mice. For analysis, Ldlr -/- (C57/Bl6) mice aged 6-8 weeks were fed a high-fat diet for 15 weeks to allow the development of atherosclerotic plaque along the aorta. Aged-matched chow-fed C57/Bl6 mice were used as athero-free controls. Aortic roots were sectioned and stained with hematoxylin and eosin, or oil red o stains, and later imaged and analyzed using ImageJ. AdipoClear and immunolabeling together with light-sheet fluorescent microscopy allowed for three-dimensional visualization. Both Imaris software v9.9.1 and the built-in bridge to ImageJ/Labkit were used to quantify the plaque burden in the mice manually or automatically, respectively. Our findings indicate that Labkit offers an effective and user-friendly platform for the segmentation of atherosclerotic plaque in aortas.
Publisher: Royal Society of Chemistry (RSC)
Date: 2022
DOI: 10.1039/D1BM01421H
Abstract: Antioxidant Response Activating nanoParticles (ARAPas), but not un-targeted drug, induce protective genes in atherosclerotic plaque.
Publisher: Cold Spring Harbor Laboratory
Date: 02-01-2020
DOI: 10.1101/2020.01.02.893065
Abstract: Assessment of preclinical models of vascular disease are paramount in the successful translation of novel treatments. The results of these models have traditionally relied on 2-D histological methodologies. Light sheet fluorescence microscopy (LSFM) is an imaging platform that allows for 3-D visualization of whole organs and tissues. In this study, we describe an improved methodological approach utilizing LSFM for imaging of preclinical vascular injury models while minimizing analysis bias. The rat carotid artery segmental pressure-controlled balloon injury and mouse carotid artery ligation injury were performed. Arteries were harvested and processed for LSFM imaging and 3-D analysis, as well as for 2-D area histological analysis. Artery processing for LSFM imaging did not induce vessel shrinkage or expansion, and was reversible by rehydrating the artery, allowing for subsequent sectioning and histological staining a posteriori . By generating a volumetric visualization along the length of the arteries, LSFM imaging provided different analysis modalities including volumetric, area, and radial parameters. Thus, LSFM-imaged arteries provided more precise measurements compared to classic histological analysis. Furthermore, LSFM provided additional information as compared to 2-D analysis in demonstrating remodeling of the arterial media in regions of hyperplasia and periadventitial neovascularization around the ligated mouse artery. LSFM provides a novel and robust 3-D imaging platform for visualizing and quantifying arterial injury in preclinical models. When compared with classic histology, LSFM outperformed traditional methods in precision and quantitative capabilities. LSFM allows for more comprehensive quantitation as compared to traditional histological methodologies, while minimizing user bias associated with area analysis of alternating, 2-D histological artery cross-sections. A more reproducible and robust quantitation of vascular pathology in preclinical models is necessary to accelerate translational discovery. Current methodology to assess vascular disease has significant limitations. The methodology described herein employs a modern imaging modality, light sheet fluorescence microscopy (LSFM), to improve assessment of established preclinical vascular injury models. LSFM provides more comprehensive and precise analysis capabilities than classical histological approaches. Hence, LSFM applied to vascular research has the potential to drive new basic discoveries, and ultimately translation of novel therapies.
Publisher: Cold Spring Harbor Laboratory
Date: 11-06-2020
DOI: 10.1101/2020.06.10.144451
Abstract: Atherosclerotic vascular disease is the leading cause of death world-wide with few novel therapies available in spite of the ongoing health burden. Oxidative stress is a well-established driver of atherosclerotic progression however the clinical translation of redox-based therapies is lacking. One of the challenges facing redox-based therapies is their targeted delivery to cellular domains of redox dysregulation. In the current study we sought to develop NPs encapsulating redox-based interventions that exploit passive means of targeting to selectively accumulate in atherosclerotic plaque with the aim of enhancing the intra-plaque bioavailability of interventions. Herein we present two types of nanoparticles (NPs): (i) We have employed flash nanoprecipitation to synthesize polymeric NPs encapsulating the hydrophobic Nrf2 activator drug, CDDO-Methyl, (ii) we have generated LDL-like NPs encapsulating the anti-inflammatory compound, oleic acid (OA). Nrf2-activators are a promising class of redox-active drug molecules whereby activation of Nrf2 results in the expression of several antioxidant and cyto-protective enzymes. Moreover, local activation of Nrf2 within the atherosclerotic plaque can be athero-protective. In this study we characterize the physiochemical properties of these NPs as well as confirm in vitro association of NPs with murine macrophages. In vitro drug release of CDDO-Me from polymeric NPs was determined by Nrf2-ARE-driven GFP fluorescence. In vivo localization was assessed through immunofluorescence of histological sections as well as whole-tissue light sheet fluorescence microscopy. We show that CDDO-Me-NPs and LDL-OA-NPs selectively accumulate in atherosclerotic plaque of two widely-used murine models of atherosclerosis: ApoE -/- and LDLr -/- mice. Overall, these studies underline that targeting of atherosclerotic plaque is an effective means to enhance delivery of redox-based interventions. Future work will assess the therapeutic efficacy of intra-plaque Nrf2 activation or anti-inflammatory actions with CDDO-Me-NPs or LDL-OA-NPs, respectively.
Publisher: Oxford University Press (OUP)
Date: 13-02-2020
DOI: 10.1093/CVR/CVAA037
Abstract: Assessment of preclinical models of vascular disease is paramount in the successful translation of novel treatments. The results of these models have traditionally relied on two-dimensional (2D) histological methodologies. Light sheet fluorescence microscopy (LSFM) is an imaging platform that allows for three-dimensional (3D) visualization of whole organs and tissues. In this study, we describe an improved methodological approach utilizing LSFM for imaging of preclinical vascular injury models while minimizing analysis bias. The rat carotid artery segmental pressure-controlled balloon injury and mouse carotid artery ligation injury were performed. Arteries were harvested and processed for LSFM imaging and 3D analysis, as well as for 2D area histological analysis. Artery processing for LSFM imaging did not induce vessel shrinkage or expansion and was reversible by rehydrating the artery, allowing for subsequent sectioning and histological staining a posteriori. By generating a volumetric visualization along the length of the arteries, LSFM imaging provided different analysis modalities including volumetric, area, and radial parameters. Thus, LSFM-imaged arteries provided more precise measurements compared to classic histological analysis. Furthermore, LSFM provided additional information as compared to 2D analysis in demonstrating remodelling of the arterial media in regions of hyperplasia and periadventitial neovascularization around the ligated mouse artery. LSFM provides a novel and robust 3D imaging platform for visualizing and quantifying arterial injury in preclinical models. When compared with classic histology, LSFM outperformed traditional methods in precision and quantitative capabilities. LSFM allows for more comprehensive quantitation as compared to traditional histological methodologies, while minimizing user bias associated with area analysis of alternating, 2D histological artery cross-sections.
Publisher: Springer Science and Business Media LLC
Date: 27-06-2019
Location: United States of America
Location: United States of America
Location: United States of America
Location: United States of America
No related grants have been discovered for Edward Bahnson.