Fig. 6.
CD47 regulation of nitric oxide signaling in vascular cells. TSP1 signaling through CD47 redundantly inhibits NO signaling that the level of eNOS, sGC, and cGK. This blocks signaling initiated by upstream calcium- and phosphorylation-mediated activation of eNOS as well as activation by exogenous NO, sGC activating drugs or phosphodiesterase inhibitors, or the direct cGK activator 8-bromo-cGMP. By dissociating the lateral interaction of CD47 with VEGFR2, TSP1 further inhibits upstream signals that activate eNOS and globally inhibits NO-independent branches of the VEGFR2 signaling cascade.
