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Lookup NU author(s): Dr Maria Camacho EncinaORCiD, Dr Rachael Redgrave, Professor Gavin RichardsonORCiD
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Introduction Due to the association of ageing with adverse myocardial remodelling and declined myocardial function, hearts from donors over 65 years of age, accounting for approximately 40% of potential adult donors, are discarded for transplant without any assessment of condition or function. Despite this association, it has been shown that ageing is not directly causal to the pathophysiology. Rather, with increasing age, myocardial remodelling and dysfunction occur, due to an accumulation of cellular stress, myocardial senescence, and expression of the senescence-associated secretory phenotype (SASP). This project aims to validate the correlation of myocardial senescence and SASP with myocardial remodelling and myocardial function to identify novel biomarkers of myocardial “health” and biological age that indicate when an older donor heart is suitable for transplantation. Results and Methods Pilot studies from 8 donor myocardial samples covering a range of normality have shown a significant correlation between the senescent cell marker p21 and biomarkers of cardiovascular disease (CVD) at the RNA level, such as Brain-type natriuretic peptide (BNP) (figure 1). Further, we have identified that myocardial SASP proteins detected in our mouse models are conserved in humans and correlate with myocardial senescence (figure 2), raising the exciting possibility that circulating myocardial SASP may represent a strong candidate for a biomarker of myocardial health. We will now expand our studies to test this correlation between myocardial senescence and myocardial remodelling in human cardiac tissue and identify if circulating SASP proteins can be used as a surrogate indicator of myocardial senescence, myocardial remodelling, and transplant outcome, in a larger cohort. For this purpose, we will use a unique source of human donor tissues and blood samples, obtained by the NHS Blood and Transplant (NHS-BT) sponsored Quality and Safety in Organ Donation Tissue Bank (QUOD).Implications The data obtained from this project has the potential to improve transplantation outcomes and increase the available donor pool by providing safe use of older donor hearts.
Author(s): Camacho Encina M, Tyler A, Hardwick I, Booth L, Redgrave R, Richardson GD
Publication type: Article
Publication status: Published
Journal: Heart
Year: 2023
Volume: 109
Issue: Supp. 3
Pages: A288-A289
Print publication date: 06/06/2023
Online publication date: 02/06/2023
Acceptance date: 02/06/2023
ISSN (print): 1355-6037
ISSN (electronic): 1468-201X
Publisher: BMJ Publishing Group
URL: http://dx.doi.org/10.1136/heartjnl-2023-BCS.271
DOI: 10.1136/heartjnl-2023-BCS.271
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