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. 2017 May 4;113(8):858–868. doi: 10.1093/cvr/cvx094

Figure 2.

Figure 2

Thrombospondin-1 in PH. Hypoxia inducible factor-2α (HIF-2α) targets hypoxia response elements (HRE) to increase THSP1 transcription in pulmonary vascular cells. In pulmonary arterial endothelial cells (PAEC) TSP1 via CD47 promotes PH by (1) targeting Cav-1 to dysregulate eNOS while increasing ROS, (2) suppressing cMyc to de-repress ET-1/ETA, and (3) decreasing cell-cell adhesion. TSP1 also increases pulmonary smooth muscle cell (PASMC) migration and fibroblast (PAFIB) activity. In pulmonary arteries, TSP1 inhibits vasorelaxation, increases vasoconstriction and in hypoxia decreases Kv1.5 ion channel effects.