| First Author | Isenberg JS | Year | 2007 |
| Journal | Blood | Volume | 109 |
| Issue | 5 | Pages | 1945-52 |
| PubMed ID | 17082319 | Mgi Jnum | J:145359 |
| Mgi Id | MGI:3834344 | Doi | 10.1182/blood-2006-08-041368 |
| Citation | Isenberg JS, et al. (2007) Thrombospondin-1 limits ischemic tissue survival by inhibiting nitric oxide-mediated vascular smooth muscle relaxation. Blood 109(5):1945-52 |
| abstractText | The nitric oxide (NO)/cGMP pathway, by relaxing vascular smooth muscle cells, is a major physiologic regulator of tissue perfusion. We now identify thrombospondin-1 as a potent antagonist of NO for regulating F-actin assembly and myosin light chain phosphorylation in vascular smooth muscle cells. Thrombospondin-1 prevents NO-mediated relaxation of precontracted vascular smooth muscle cells in a collagen matrix. Functional magnetic resonance imaging demonstrated that an NO-mediated increase in skeletal muscle perfusion was enhanced in thrombospondin-1-null relative to wild-type mice, implicating endogenous thrombospondin-1 as a physiologic antagonist of NO-mediated vasodilation. Using a random myocutaneous flap model for ischemic injury, tissue survival was significantly enhanced in thrombospondin-1-null mice. Improved flap survival correlated with increased recovery of oxygen levels in the ischemic tissue of thrombospondin-1-null mice as measured by electron paramagnetic resonance oximetry. These findings demonstrate an important antagonistic relation between NO/cGMP signaling and thrombospondin-1 in vascular smooth muscle cells to regulate vascular tone and tissue perfusion. |
