Increasing survival of ischemic tissue by targeting CD47
Increasing survival of ischemic tissue by targeting CD47
复制标题
DOI：
10.1161/01.res.0000259579.35787.4e
复制
发表时间：
2007-03-16
影响因子：
20.1
通讯作者：
Roberts, David D.
中科院分区：
文献类型：
--
作者：
Isenberg, Jeff S.;Romeo, Martin J.;Roberts, David D.
血小板反应蛋白-1（TSP 1）限制NO的血管生成和血管扩张活性。TSP 1的这种活性在某些疾病状态下可能是有益的，但内源性TSP 1限制了小鼠背部皮瓣固定缺血损伤后组织灌注的恢复。使用缺乏TSP 1受体CD 36或CD 47的小鼠，我们现在表明CD 47是限制皮瓣和后肢缺血性损伤后NO介导的血管平滑肌松弛和组织存活的必要受体。我们进一步表明，使用单克隆抗体阻断CD 47或TSP 1和使用反义吗啉代寡核苷酸降低CD 47表达是有效的治疗方法，以显着增加遭受固定缺血的软组织的存活率。这些治疗促进快速血管重塑以恢复组织灌注并增加皮肤和肌肉活力。因此，限制NO介导的血管舒张和血管重塑的CD 47依赖性拮抗作用是一种有前途的治疗方式，以保护组织缺血应激。
Thrombospondin-1 (TSP1) limits the angiogenic and vasodilator activities of NO. This activity of TSP1 can be beneficial in some disease states, but endogenous TSP1 limits recovery of tissue perfusion following fixed ischemic injury in dorsal skin flaps in mice. Using mice lacking the TSP1 receptors CD36 or CD47, we now show that CD47 is the necessary receptor for limiting NO-mediated vascular smooth muscle relaxation and tissue survival following ischemic injury in skin flaps and hindlimbs. We further show that blocking CD47 or TSP1 using monoclonal antibodies and decreasing CD47 expression using an antisense morpholino oligonucleotide are effective therapeutic approaches to dramatically increase survival of soft tissue subjected to fixed ischemia. These treatments facilitate rapid vascular remodeling to restore tissue perfusion and increase skin and muscle viability. Thus, limiting CD47-dependent antagonism of NO-mediated vasodilation and vascular remodeling is a promising therapeutic modality to preserve tissues subject to ischemic stress.