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Moreover, Tat is released by acutely HIV-infected cells via a leaderless secretory pathway and in a biologically active form that exerts effects on both HIV-infected and uninfected cells from different organs and systems. This review focuses on the activities of extracellular Tat protein on endothelial cells, on angiogenesis, and on the pathogenesis of AIDS-associated angioproliferative diseases such as Kaposi's sarcoma. 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