A study protocol to characterise pathophysiological and molecular markers of rheumatic heart disease and degenerative aortic stenosis using multiparametric cardiovascular imaging and multiomics techniques.

Autor: Mutithu DW; Department of Medicine, Cape Heart Institute, University of Cape Town, Cape Town, South Africa.; Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.; Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, South African Medical Research Council, Cape Town, South Africa., Aremu OO; Department of Medicine, Cape Heart Institute, University of Cape Town, Cape Town, South Africa.; Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.; Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, South African Medical Research Council, Cape Town, South Africa., Mokaila D; Department of Medicine, Cape Heart Institute, University of Cape Town, Cape Town, South Africa.; Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.; Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, South African Medical Research Council, Cape Town, South Africa., Bana T; Department of Medicine, Cape Heart Institute, University of Cape Town, Cape Town, South Africa.; Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.; Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, South African Medical Research Council, Cape Town, South Africa., Familusi M; Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.; Department of Civil Engineering, University of Cape Town, Cape Town, South Africa., Taylor L; Division of Forensic Medicine and Toxicology, Department of Pathology, University of Cape Town, Cape Town, South Africa., Martin LJ; Division of Forensic Medicine and Toxicology, Department of Pathology, University of Cape Town, Cape Town, South Africa., Heathfield LJ; Division of Forensic Medicine and Toxicology, Department of Pathology, University of Cape Town, Cape Town, South Africa., Kirwan JA; Metabolomics Platform, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany.; Max-Delbrück-Center (MDC) for Molecular Medicine, Helmholtz Association, Berlin, Germany., Wiesner L; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Adeola HA; Division of Dermatology, Department of Medicine, University of Cape Town, Cape Town, South Africa., Lumngwena EN; Department of Medicine, Cape Heart Institute, University of Cape Town, Cape Town, South Africa.; Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.; Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, South African Medical Research Council, Cape Town, South Africa.; School of Clinical Medicine, University of the Witwatersrand, Johannesburg, South Africa., Manganyi R; Chris Barnard Division of Cardiothoracic Surgery, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa., Skatulla S; Department of Civil Engineering, University of Cape Town, Cape Town, South Africa., Naidoo R; Division of Anatomical Pathology, Department of Pathology, University of Cape Town and National Health Laboratory Service, Cape Town, South Africa., Ntusi NAB; Department of Medicine, Cape Heart Institute, University of Cape Town, Cape Town, South Africa.; Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.; Extramural Unit on Intersection of Noncommunicable Diseases and Infectious Diseases, South African Medical Research Council, Cape Town, South Africa.; Cape Universities Body Imaging Centre, University of Cape Town, Cape Town, South Africa.; Wellcome Centre for Infectious Disease Research, University of Cape Town, Cape Town, South Africa.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 May 13; Vol. 19 (5), pp. e0303496. Date of Electronic Publication: 2024 May 13 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0303496
Abstrakt: Introduction: Rheumatic heart disease (RHD), degenerative aortic stenosis (AS), and congenital valve diseases are prevalent in sub-Saharan Africa. Many knowledge gaps remain in understanding disease mechanisms, stratifying phenotypes, and prognostication. Therefore, we aimed to characterise patients through clinical profiling, imaging, histology, and molecular biomarkers to improve our understanding of the pathophysiology, diagnosis, and prognosis of RHD and AS.
Methods: In this cross-sectional, case-controlled study, we plan to recruit RHD and AS patients and compare them to matched controls. Living participants will undergo clinical assessment, echocardiography, CMR and blood sampling for circulatory biomarker analyses. Tissue samples will be obtained from patients undergoing valve replacement, while healthy tissues will be obtained from cadavers. Immunohistology, proteomics, metabolomics, and transcriptome analyses will be used to analyse circulatory- and tissue-specific biomarkers. Univariate and multivariate statistical analyses will be used for hypothesis testing and identification of important biomarkers. In summary, this study aims to delineate the pathophysiology of RHD and degenerative AS using multiparametric CMR imaging. In addition to discover novel biomarkers and explore the pathomechanisms associated with RHD and AS through high-throughput profiling of the tissue and blood proteome and metabolome and provide a proof of concept of the suitability of using cadaveric tissues as controls for cardiovascular disease studies.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2024 Mutithu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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