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. Author manuscript; available in PMC: 2019 Jan 1.
Published in final edited form as: Blood Rev. 2017 Aug 16;32(1):61–70. doi: 10.1016/j.blre.2017.08.008

Figure 1. PlGF-mediated activation of HiF-1α and downstream activation of target genes in monocytes and endothelial cells.

Figure 1

Due to increased erythropoiesis in SCD as a compensatory response to severe hemolytic anemia, Erythropoietin (Epo) is released at high levels which targets erythroid cells to secrete PlGF. Released PlGF in circulation can target blood cells, e.g. MNCs and vascular endothelium (endothelial cells). PlGF causes activation of HIF-1α, independent of hypoxia and stimulates expression of cytochemokines, leukotriene formation via activation of lipoxygenase enzymes, and expression of ET-1 and PAI-1, the latter is involved in pulmonary hypertension in SCD.