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      Cardiovascular Mechano-Epigenetics: Force-Dependent Regulation of Histone Modifications and Gene Regulation

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          Abstract

          The local mechanical microenvironment impacts on the cell behavior. In the cardiovascular system, cells in both the heart and the vessels are exposed to continuous blood flow, blood pressure, stretching forces, and changing extracellular matrix stiffness. The force-induced signals travel all the way to the nucleus regulating epigenetic changes such as chromatin dynamics and gene expression. Mechanical cues are needed at the very early stage for a faultless embryological development, while later in life, aberrant mechanical signaling can lead to a range of pathologies, including diverse cardiovascular diseases. Hence, an investigation of force-generated epigenetic alteration at different time scales is needed to understand fully the phenotypic changes in disease onset and progression. That being so, cardiovascular mechano-epigenetics emerges as an attractive field of study. Given the rapid advances in this emergent field of research, this short review aims to provide an analysis of the state of knowledge of force-induced epigenetic changes in the cardiovascular field.

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          Drug repurposing: progress, challenges and recommendations

          Sudeep Pushpakom, Francesco Iorio, Patrick A. Eyers … (2018)
          Given the high attrition rates, substantial costs and slow pace of new drug discovery and development, repurposing of 'old' drugs to treat both common and rare diseases is increasingly becoming an attractive proposition because it involves the use of de-risked compounds, with potentially lower overall development costs and shorter development timelines. Various data-driven and experimental approaches have been suggested for the identification of repurposable drug candidates; however, there are also major technological and regulatory challenges that need to be addressed. In this Review, we present approaches used for drug repurposing (also known as drug repositioning), discuss the challenges faced by the repurposing community and recommend innovative ways by which these challenges could be addressed to help realize the full potential of drug repurposing.
          Article 0 comments Cited 1024 times – based on 0 reviews     Review now
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            CUT&Tag for efficient epigenomic profiling of small samples and single cells

            Hatice Kaya-Okur, Steven J. Wu, Christine Codomo … (2019)
            Many chromatin features play critical roles in regulating gene expression. A complete understanding of gene regulation will require the mapping of specific chromatin features in small samples of cells at high resolution. Here we describe Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tethering strategy that provides efficient high-resolution sequencing libraries for profiling diverse chromatin components. In CUT&Tag, a chromatin protein is bound in situ by a specific antibody, which then tethers a protein A-Tn5 transposase fusion protein. Activation of the transposase efficiently generates fragment libraries with high resolution and exceptionally low background. All steps from live cells to sequencing-ready libraries can be performed in a single tube on the benchtop or a microwell in a high-throughput pipeline, and the entire procedure can be performed in one day. We demonstrate the utility of CUT&Tag by profiling histone modifications, RNA Polymerase II and transcription factors on low cell numbers and single cells.
            Article 0 comments Cited 591 times – based on 0 reviews     Review now
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              Vascular smooth muscle cells in atherosclerosis

              Gemma Basatemur, Helle Jørgensen, Murray Clarke … (2019)
              Vascular smooth muscle cells (VSMCs) are a major cell type present at all stages of an atherosclerotic plaque. According to the 'response to injury' and 'vulnerable plaque' hypotheses, contractile VSMCs recruited from the media undergo phenotypic conversion to proliferative synthetic cells that generate extracellular matrix to form the fibrous cap and hence stabilize plaques. However, lineage-tracing studies have highlighted flaws in the interpretation of former studies, revealing that these studies had underestimated both the content and functions of VSMCs in plaques and have thus challenged our view on the role of VSMCs in atherosclerosis. VSMCs are more plastic than previously recognized and can adopt alternative phenotypes, including phenotypes resembling foam cells, macrophages, mesenchymal stem cells and osteochondrogenic cells, which could contribute both positively and negatively to disease progression. In this Review, we present the evidence for VSMC plasticity and summarize the roles of VSMCs and VSMC-derived cells in atherosclerotic plaque development and progression. Correct attribution and spatiotemporal resolution of clinically beneficial and detrimental processes will underpin the success of any therapeutic intervention aimed at VSMCs and their derivatives.
              Article 0 comments Cited 343 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Thomas Iskratsch:
                ORCID: http://orcid.org/0000-0002-3738-7830
                t.iskratsch@qmul.ac.uk
                Journal
                Journal ID (nlm-ta): Cardiovasc Drugs Ther
                Journal ID (iso-abbrev): Cardiovasc Drugs Ther
                Title: Cardiovascular Drugs and Therapy
                Publisher: Springer US (New York )
                ISSN (Print): 0920-3206
                ISSN (Electronic): 1573-7241
                Publication date (Electronic): 18 January 2023
                Publication date PMC-release: 18 January 2023
                Publication date (Print): 2024
                Volume: 38
                Issue: 2
                Pages: 215-222
                Affiliations
                School of Engineering and Materials Science, Queen Mary University of London, ( https://ror.org/026zzn846) London, UK
                Author information
                http://orcid.org/0000-0002-3738-7830
                Article
                Publisher ID: 7422
                DOI: 10.1007/s10557-022-07422-z
                PMC ID: 10959834
                PubMed ID: 36653625
                SO-VID: 954f8b2a-7076-4683-acc0-ae45dcacb92e
                Copyright © © The Author(s) 2023
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date accepted : 28 December 2022
                Funding
                Funded by: British Heart Foundation
                Award ID: PG/20/6/34835
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100000268, Biotechnology and Biological Sciences Research Council;
                Award ID: BB/S001123/1
                Award Recipient :
                Categories
                Subject: Invited: Bscr Marshall Submissions
                Custom metadata
                issue-copyright-statement © Springer Science+Business Media, LLC, part of Springer Nature 2024

                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: cardiovascular diseases,mechanobiology,mechano-epigenetics,histone modifications
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine
                Keywords: cardiovascular diseases, mechanobiology, mechano-epigenetics, histone modifications

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