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1.
Rheumatol Immunol Res ; 5(2): 99-106, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39015844

RESUMO

Systemic sclerosis is a multisystemic disease for which the heart can be affected leading to cardiac complications and mortality. Up to 80% of patients with systemic sclerosis have cardiac involvement with varying levels of severity. Several molecules have been identified that can be used as markers of cardiac involvement. These biomarkers can arise directly from the heart due to cardiac damage from the disease such as cardiac troponins or from the underlying dysregulated immune process itself such as the proinflammatory cytokines including interleukin (IL)-6. This review aims to summarize the evidence on currently known biomarkers that are can be diagnostic, prognostic or predictive of primary cardiac involvement in systemic sclerosis. We also highlight potential new biomarkers based on the current understanding of the disease process. Clinical use of these markers can benefit patients through earlier identification of those with cardiac involvement, many of whom can be asymptomatic in the early stage, with higher risk of complications, with the overall goal to improve outcomes of these affected patients.

2.
Blood ; 133(21): 2325-2337, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-30755421

RESUMO

Dengue virus (DENV) is the most prevalent vector-borne viral pathogen, infecting millions of patients annually. Thrombocytopenia, a reduction in circulating platelet counts, is the most consistent sign of DENV-induced disease, independent of disease severity. However, the mechanisms leading to DENV-induced thrombocytopenia are unknown. Here, we show that thrombocytopenia is caused by serotonin derived from mast cells (MCs), which are immune cells that are present in the perivascular space and are a major peripheral source of serotonin. We show that during DENV infection, MCs release serotonin, which prompts platelet activation, aggregation, and enhanced phagocytosis, dependent on 5HT2A receptors. MC deficiency in mice or pharmacologic inhibition of MCs reversed thrombocytopenia. Furthermore, reconstitution of MC-deficient mice with wild-type MCs, but not MCs lacking serotonin synthesis resulting from deficiency in the enzyme tryptophan hydroxylase-1, restored the thrombocytopenic phenotype. Exogenous serotonin was also sufficient to overcome the effects of drugs that inhibit platelet activation in vitro and to restore thrombocytopenia in DENV-infected MC-deficient mice. Therapeutic targeting of 5HT2A receptors during DENV infection effectively prevented thrombocytopenia in mice. Similarly, serotonin derived from DENV-activated human MCs led to increased human platelet activation. Thus, MC-derived serotonin is a previously unidentified mechanism of DENV-induced thrombocytopenia and a potential therapeutic target.


Assuntos
Plaquetas/metabolismo , Vírus da Dengue/metabolismo , Dengue/metabolismo , Ativação Plaquetária , Receptor 5-HT2A de Serotonina/metabolismo , Serotonina/metabolismo , Trombocitopenia/metabolismo , Animais , Plaquetas/patologia , Dengue/genética , Dengue/patologia , Feminino , Humanos , Masculino , Mastócitos/patologia , Camundongos , Camundongos Knockout , Receptor 5-HT2A de Serotonina/genética , Serotonina/genética , Trombocitopenia/genética , Trombocitopenia/patologia , Trombocitopenia/virologia
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