Genes, autoimmunity and pathogenesis of rheumatic heart disease

Guilherme, Luiza; Köhler, KF; Postol, Edilberto; Kalil, Jorge

doi:10.4103/0974-2069.79617

Cited by 68 publications

(75 citation statements)

References 63 publications

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“…Immunohistochemistry of cardiac samples from this model revealed similar features to the acute and chronic forms of RHD. The acute and chronic forms of RHD exhibited inflammation, tissue damage, and cardiac tissue compression and shrinkage, which are primarily due to an autoimmune response (31).…”

Section: Discussionmentioning

confidence: 99%

Bmi1 and BRG1 drive myocardial repair by regulating cardiac stem cell function in acute rheumatic heart disease

Xiao

Zhang

Tao

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Rheumatic heart disease (RHD) occurs due to the accumulation of complications associated with rheumatic fever, and it results in high morbidity and mortality. The majority of cases of RHD are diagnosed in the chronic stages, when treatment options are limited. A small reservoir of cardiac stem cells is responsible for maintaining cardiac homeostasis and repairing tissue damage. Understanding the role of cardiac stem cells and the various proteins responsible for their functions in different pathological stages of RHD is an important area of investigation. Polycomb complex protein BMI-1 (Bmi1) and transcription activator BRG1 (BRG1) are associated with the maintenance of stemness in various types of stem cells. The present study investigated the role served by Bmi1 and BRG1 in cardiac stem cells during various pathological stages of RHD through immunohistochemistry and western blotting. A rat model of RHD was established via immunization with the Group A Streptococcus M5 protein.The rat was demonstrated to develop acute RHD 2 months after the final immunization, characterized by cardiac inflammation and tissue damage. Chronic RHD was identified 4 months after the final immunization, revealed by cardiac tissue compression and shrinkage. Expression of the cardiac stem cell marker mast/stem cell growth factor receptor kit was identified to be elevated during acute RHD, but downregulated in the chronic stages of RHD. A similar pattern of expression was revealed for Bmi1 and BRG1, indicating that they serve a role in regulating cardiac stem cell proliferation during acute RHD. These results suggest that cardiac stem cells serve a supportive role in the acute, but not chronic, stages of RHD via expression of Bmi1 and BRG1. IntroductionRheumatic heart disease (RHD) is a major health issue worldwide, which primarily results in cardiovascular disease and associated morbidities (1,2). RHD most frequently affects children between 5 and 14 years old (3). The diagnosis of RHD has gradually increased, particularly in the latent stage of the disease (4,5). A previous pathological study demonstrated that valvular inflammation occurs as the disease progresses, which is due to the presence of immunodominant epitopes following infection (6). There are numerous limitations including the asymptomatic nature of the disease and a lack of trained practitioners for screening RHD in the latent stage of the disease (7). In certain cases of chronic RHD, valve replacement is the only treatment option (8). The formation of rheumatic lesions and Aschoff bodies are indicative of the active form of RHD (9-11).Cardiac stem cells have the ability to convert fibrotic scars, which are formed through injury or inflammation, into nascent cardiomyocytes (12). Cardiomyocytes have a low turnover, which reflects the small reservoir of cardiac stem cells (13). The underlying molecular mechanisms of the self-renewal, potency and survival abilities of cardiac stem cells remain unclear and require further study (14). A number of biomarkers are used ...

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Section: Discussionmentioning

confidence: 99%

Bmi1 and BRG1 drive myocardial repair by regulating cardiac stem cell function in acute rheumatic heart disease

Xiao

Zhang

Tao

et al. 2017

Experimental and Therapeutic Medicine

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“…In Sudan, surgical outcomes are expected to be even worse due to multiple factors including poor compliance with both anticoagulation and penicillin prophylaxis, disease progression/recurrence and the social Similar factors may contribute to the high burden and aggressive disease patterns of RHD in Al Fashir. In addition, genetic susceptibility, which is a known factor that determines RHD, may have a role in the pattern of the disease in this area [9]. However, the most crucial factor that contributed to this catastrophic pattern is the lack of a Ministry of Health-based organised control program together with the weakness of the primary healthcare system.…”

Section: Discussionmentioning

confidence: 99%

Rheumatic heart disease in North Darfur: an alarmingly high burden and control initiative

et al. 2018

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Rheumatic heart disease (RHD) is the most common cause of cardiac morbidity in Sudanese young people and it is particularly prevalent in Darfur area. A retrospective review of clinical and echocardiography (echo) data for children with RHD seen in Al Fashir Hospital from 2010 to 2016 was conducted. Data from the hospital statistics, outpatient and echo clinic records were collected and analysed. A control program was started based on training modules and public awareness material. In the study period, 324 patients were admitted and 3,777 patients with RHD were seen in outpatient clinics. Complications occurred in 33% of inpatients with a case fatality of 12%. Echo revealed that 83% of patients have severe disease and 50% have a combination of more than two valves affected. Training of 50 medical assistants, 30 physicians and 10 health promoters was achieved. Public awareness programs were conducted. We found a significant burden of RHD in Al Fashir Hospital. A control program was initiated that needs substantial support from governmental and nongovernmental organizations.

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“…It is extremely difficult to identify the specific causes of autoimmunity in individual patients, as it usually has contributions from a number of internal and external factors, including a genetic predisposition, age, previous immune challenges, exposure to pathogens etc., [6][7][8][9]. Even though genetic predisposition is known to play a very significant role, it is believed that some additional environmental triggers are required for the onset of autoimmunity, and these are usually represented by infections [10,11].…”

Section: Introductionmentioning

confidence: 99%

Effects of Viral and Cytokine Delays on Dynamics of Autoimmunity

Chenar¹,

Kyrychko²,

Blyuss³

2018

Mathematics

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Abstract:A major contribution to the onset and development of autoimmune disease is known to come from infections. An important practical problem is identifying the precise mechanism by which the breakdown of immune tolerance as a result of immune response to infection leads to autoimmunity. In this paper, we develop a mathematical model of immune response to a viral infection, which includes T cells with different activation thresholds, regulatory T cells (Tregs), and a cytokine mediating immune dynamics. Particular emphasis is made on the role of time delays associated with the processes of infection and mounting the immune response. Stability analysis of various steady states of the model allows us to identify parameter regions associated with different types of immune behaviour, such as, normal clearance of infection, chronic infection, and autoimmune dynamics. Numerical simulations are used to illustrate different dynamical regimes, and to identify basins of attraction of different dynamical states. An important result of the analysis is that not only the parameters of the system, but also the initial level of infection and the initial state of the immune system determine the progress and outcome of the dynamics.

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Genes, autoimmunity and pathogenesis of rheumatic heart disease

Cited by 68 publications

References 63 publications

Bmi1 and BRG1 drive myocardial repair by regulating cardiac stem cell function in acute rheumatic heart disease

Bmi1 and BRG1 drive myocardial repair by regulating cardiac stem cell function in acute rheumatic heart disease

Rheumatic heart disease in North Darfur: an alarmingly high burden and control initiative

Effects of Viral and Cytokine Delays on Dynamics of Autoimmunity

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