Figure 1.

Thrombospondin-1 negatively intersects vascular NO-ROS. Under healthy conditions TSP1 is almost undetectable. In acute and chronic injury and disease, TSP1 is induced in the systemic vasculature to engage CD47 and limit NO signaling through decreasing eNOS activity, and separately by rendering sGC and PKG resistant to activation. Separately, TSP1 limits cAMP signaling. TSP1 also activates NADPH oxidase 1 (Nox1) increasing superoxide production. Acting via these several pathways TSP1 promotes vascular rarefaction, vasoconstriction and ischaemia.