The Journal of clinical investigation
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This study reports on what we believe are novel mechanism(s) of the vascular protective action of adiponectin. We used intravital microscopy to measure leukocyte-endothelium interactions in adiponectin-deficient (Ad(-/-)) mice and found that adiponectin deficiency was associated with a 2-fold increase in leukocyte rolling and a 5-fold increase in leukocyte adhesion in the microcirculation. Measurement of endothelial NO (eNO) revealed that adiponectin deficiency drastically reduced levels of eNO in the vascular wall. ⋯ Mechanistically, blockade of eNOS with N(omega)-nitro-L-arginine methyl ester ( L-NAME) abolished the inhibitory effect of gAd on leukocyte adhesion, demonstrating the obligatory role of eNOS signaling in the antiinflammatory action of gAd. We believe this is the first demonstration that gAd protects the vasculature in vivo via increased NO bioavailability with suppression of leukocyte-endothelium interactions. Overall, we provide evidence that loss of adiponectin induces a primary state of endothelial dysfunction with increased leukocyte-endothelium adhesiveness.
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In this issue of the JCI, Wang, Clemens, and colleagues demonstrate that hypoxia-inducible factor alpha (HIF alpha) signaling in bone-building osteoblasts is central to the coupling of angiogenesis and long bone development in mice (see the related article beginning on page 1616). They show that bone formation controlled by osteoblast HIF alpha signaling is not cell autonomous but is coupled to skeletal angiogenesis dependent upon VEGF signaling. Thus, strategies that promote HIF alpha signaling in osteoblasts may augment bone formation and accelerate fracture repair.