ORCID Profile
0000-0003-4125-6232
Current Organisation
University of North Carolina at Chapel Hill
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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: 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: Springer Science and Business Media LLC
Date: 27-06-2019
Location: United States of America
No related grants have been discovered for Ana Cartaya.