Abstract
Cardiac sarcoidosis (CS) is a poorly understood disease and is characterized by the focal accumulation of immune cells, thus leading to the formation of granulomata (GL). To identify the developmental principles of fatal GL, fluorescence microscopy and Western blot analysis of CS and control patients is presented here. CS is visualized macroscopically by positron emission tomography (PET)/ computed tomography (CT). A battery of antibodies is used to determine structural, cell cycle and inflammatory markers. GL consist of CD68+, CD163+ and CD206+ macrophages surrounded by T-cells within fibrotic areas. Cell cycle markers such as phospho-histone H3, phospho-Aurora and Ki67 were moderately present; however, the phosphorylated ERM (ezrin, radixin and moesin) and Erk1/2 proteins, strong expression of the myosin motor protein and the macrophage transcription factor PU.1 indicate highly active GL. Mild apoptosis is consistent with PI3 kinase and Akt activation. Massive amounts of the IL-1R antagonist reflect a mild activation of stress and inflammatory pathways in GL. High levels of oncostatin M and the Reg3A and Reg3γ chemokines are in accordance with macrophage accumulation in areas of remodeling cardiomyocytes. We conclude that the formation of GL occurs mainly through chemoattraction and less by proliferation of macrophages. Furthermore, activation of the oncostatin/Reg3 axis might help at first to wall-off substances but might initiate the chronic development of heart failure.
Highlights
Systemic sarcoidosis is a rare granulomatous disease with a prevalence of 5–64 per 100,000 people and can vary considerably between ethnic groups, regions, sex and age [1,2]
The healing effects of available treatments can vary between organs and tissues, indicating that various signaling cascades might be involved to different degrees in the development of sarcoidosis and its progression [7]
Since increased glucose metabolism is regarded as an indicator of inflammation, an increased uptake of the glucose analog 18F-FDG was visualized by a positron emission tomography (PET)/computed tomography (CT) [8] (Figure 1B)
Summary
Systemic sarcoidosis is a rare granulomatous disease with a prevalence of 5–64 per 100,000 people and can vary considerably between ethnic groups, regions, sex and age [1,2]. It is regarded as an autoimmune disease triggered by the exposure of genetically susceptible individuals to antigens and affects various organs and tissues, especially lymph nodes, skin, eyes, and lungs. The healing effects of available treatments can vary between organs and tissues, indicating that various signaling cascades might be involved to different degrees in the development of sarcoidosis and its progression [7]
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