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• W2023722538 abstract "Primary human microvascular endothelial cells (MVEC) of restricted lineage undergo apoptosis when exposed to plasma from patients with thrombotic thrombocytopenic purpura (TTP) and sporadic hemolytic-uremic syndrome (HUS). This reflects the pathology and tissue distribution of lesions in vivo. As extracellular matrix (ECM) is critical to MVEC survival, and cytokines which regulate ECM, such as transforming growth factor (TGF)-beta1, have been reported anecdotally to be altered in TTP/HUS, we examined the role of TGF-beta1 and two ECM proteins, fibronectin and thrombospondin (TSP), in these disorders. Levels of active TGF-beta1 were elevated in acute but not convalescent phases of TTP/sporadic HUS, as well as TTP associated with human immunodeficiency virus infection and use of the anti-platelet drug ticlopidine. MVEC from tissues susceptible to TTP-mediated apoptosis showed little active TGF-beta1 production when exposed to TTP plasmas. In contrast, pulmonary MVEC and large-vessel EC, which are resistant to TTP-linked pathology, showed marked induction of TGF-beta1 following TTP plasma exposure. Exogenous TGF-beta1 suppressed TTP plasma-mediated apoptosis in susceptible MVEC in association with blockade of cell entry into S phase. Soluble TSP, devoid of detectable bound TGF-beta1, had a similar effect, which paralleled its ability to induce TGF-beta1 production in MVEC. In vivo, TSP deposition was diminished markedly in involved tissues of TTP patients. These data highlight the role of TGF-beta1 and ECM in TTP and suggest that differential production of TGF-beta1 by MVEC may play a role in their sensitivity or resistance to TTP/sporadic HUS-mediated apoptosis in vitro and in vivo." @default.
• W2023722538 created "2016-06-24" @default.
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• W2023722538 date "2000-01-01" @default.
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• W2023722538 title "Role of transforming growth factor ?1 in microvascular endothelial cell apoptosis associated with thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome" @default.
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• W2023722538 doi "https://doi.org/10.1002/1096-8652(200101)66:1<12::aid-ajh1001>3.0.co;2-i" @default.
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