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Mechanistic implications of altered protein expression in rheumatic heart disease.
Heart Fail Rev. 2020 Jul 11 [Online ahead of print]HF

Abstract

Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in low- and middle-income countries, where living conditions promote spread of group A β-haemolytic streptococcus. Autoimmune reactions due to molecular mimicry of bacterial epitopes by host proteins cause acute rheumatic fever (ARF) and subsequent disease progression to RHD. Despite knowledge of the factors that predispose to ARF and RHD, determinants of the progression to valvular damage and the molecular events involved remain incompletely characterised. This review focuses on altered protein expression in heart valves, myocardial tissue and plasma of patients with RHD and pathogenic consequences on RHD. Proteins mainly involved in structural organization of the valve matrix, blood homeostasis and immune response were altered due to RHD pathogenesis. Study of secreted forms of these proteins may aid the development of non-invasive biomarkers for early diagnosis and monitoring outcomes in RHD. Valve replacement surgery, the single evidence-based strategy to improve outcomes in severe RHD, is costly, largely unavailable in low- and middle-income countries (LMIC) and requires specialised facilities. When diagnosed early, penicillin prophylaxis may be used to delay progression to severe valvular damage. Echocardiography and cardiovascular magnetic resonance and the standard imaging tools recommended to confirm early diagnosis remain largely unavailable and inaccessible in most LMIC and both require expensive equipment and highly skilled persons for manipulation as well as interpretation of results. Changes in protein expression in heart valves and myocardium are associated with progressive valvular deformation in RHD. Understanding these protein changes should shed more light on the mechanisms of pathogenicity, while secreted forms of these proteins may provide leads towards a biomarker for non-invasive early detection of RHD.

Authors+Show Affiliations

Division of Cardiology, Department of Medicine, Faculty of Health Sciences and Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. en.lumngwena@uct.ac.za. Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. en.lumngwena@uct.ac.za. Hatter instititute for Cardiovascualar research in Africa, Departmenent of Medicine, 4th floor Chris Barnard Building, University of Cape Town, Cape Town, South Africa. en.lumngwena@uct.ac.za. Centre for the Study of Emerging and Re-emerging Infections (CREMER), Institute for Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific Research and Innovation, Yaounde, Cameroon. en.lumngwena@uct.ac.za.Department of Civil Engineering, Faculty of Engineering and the Built Environment, University of Cape Town, Cape Town, South Africa.Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Department of Integrative Biomedical Sciences, University of Cape Town, Cape Town, South Africa.Division of Cardiology, Department of Medicine, Faculty of Health Sciences and Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa. Hatter instititute for Cardiovascualar research in Africa, Departmenent of Medicine, 4th floor Chris Barnard Building, University of Cape Town, Cape Town, South Africa. Cape Universities Body Imaging Centre, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32653980

Citation

Lumngwena, Evelyn N., et al. "Mechanistic Implications of Altered Protein Expression in Rheumatic Heart Disease." Heart Failure Reviews, 2020.
Lumngwena EN, Skatulla S, Blackburn JM, et al. Mechanistic implications of altered protein expression in rheumatic heart disease. Heart Fail Rev. 2020.
Lumngwena, E. N., Skatulla, S., Blackburn, J. M., & Ntusi, N. A. B. (2020). Mechanistic implications of altered protein expression in rheumatic heart disease. Heart Failure Reviews. https://doi.org/10.1007/s10741-020-09993-1
Lumngwena EN, et al. Mechanistic Implications of Altered Protein Expression in Rheumatic Heart Disease. Heart Fail Rev. 2020 Jul 11; PubMed PMID: 32653980.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mechanistic implications of altered protein expression in rheumatic heart disease. AU - Lumngwena,Evelyn N, AU - Skatulla,Sebastian, AU - Blackburn,Jonathan M, AU - Ntusi,Ntobeko A B, Y1 - 2020/07/11/ PY - 2020/7/13/entrez PY - 2020/7/13/pubmed PY - 2020/7/13/medline KW - Pathogenesis KW - Pathological implications KW - Protein changes KW - Proteomics KW - Rheumatic heart disease JF - Heart failure reviews JO - Heart Fail Rev N2 - Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in low- and middle-income countries, where living conditions promote spread of group A β-haemolytic streptococcus. Autoimmune reactions due to molecular mimicry of bacterial epitopes by host proteins cause acute rheumatic fever (ARF) and subsequent disease progression to RHD. Despite knowledge of the factors that predispose to ARF and RHD, determinants of the progression to valvular damage and the molecular events involved remain incompletely characterised. This review focuses on altered protein expression in heart valves, myocardial tissue and plasma of patients with RHD and pathogenic consequences on RHD. Proteins mainly involved in structural organization of the valve matrix, blood homeostasis and immune response were altered due to RHD pathogenesis. Study of secreted forms of these proteins may aid the development of non-invasive biomarkers for early diagnosis and monitoring outcomes in RHD. Valve replacement surgery, the single evidence-based strategy to improve outcomes in severe RHD, is costly, largely unavailable in low- and middle-income countries (LMIC) and requires specialised facilities. When diagnosed early, penicillin prophylaxis may be used to delay progression to severe valvular damage. Echocardiography and cardiovascular magnetic resonance and the standard imaging tools recommended to confirm early diagnosis remain largely unavailable and inaccessible in most LMIC and both require expensive equipment and highly skilled persons for manipulation as well as interpretation of results. Changes in protein expression in heart valves and myocardium are associated with progressive valvular deformation in RHD. Understanding these protein changes should shed more light on the mechanisms of pathogenicity, while secreted forms of these proteins may provide leads towards a biomarker for non-invasive early detection of RHD. SN - 1573-7322 UR - https://www.unboundmedicine.com/medline/citation/32653980/Mechanistic_implications_of_altered_protein_expression_in_rheumatic_heart_disease L2 - https://doi.org/10.1007/s10741-020-09993-1 DB - PRIME DP - Unbound Medicine ER -
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