| First Author | Ohashi K | Year | 2009 |
| Journal | Mol Cell Biol | Volume | 29 |
| Issue | 13 | Pages | 3487-99 |
| PubMed ID | 19398582 | Mgi Jnum | J:149889 |
| Mgi Id | MGI:3849341 | Doi | 10.1128/MCB.00126-09 |
| Citation | Ohashi K, et al. (2009) Adiponectin promotes revascularization of ischemic muscle through a cyclooxygenase 2-dependent mechanism. Mol Cell Biol 29(13):3487-99 |
| abstractText | Adiponectin is a fat-derived plasma protein that has cardioprotective roles in obesity-linked diseases. Because cyclooxygenase 2 (COX-2) is an important modulator of endothelial function, we investigated the possible contribution of COX-2 to adiponectin-mediated vascular responses in a mouse hind limb model of vascular insufficiency. Ischemic insult increased COX-2 expression in endothelial cells of wild-type mice, but this induction was attenuated in adiponectin knockout mice. Ischemia-induced revascularization was impaired in mice in which the Cox-2 gene is deleted in Tie2-Cre-expressing cells. Adenovirus-mediated overexpression of adiponectin enhanced COX-2 expression and revascularization of ischemic limbs in control mice, but not in targeted Cox-2-deficient mice. In cultured endothelial cells, adiponectin protein increased COX-2 expression, and ablation of COX-2 abrogated the adiponectin-stimulated increases in endothelial cell migration, differentiation, and survival. Ablation of calreticulin (CRT) or its adaptor protein CD91 diminished adiponectin-stimulated COX-2 expression and endothelial cell responses. These observations provide evidence that adiponectin promotes endothelial cell function through CRT/CD91-mediated increases in COX-2 signaling. Thus, disruption of the adiponectin-COX-2 regulatory axis in endothelial cells could participate in the pathogenesis of obesity-related vascular diseases. |
