Bone Marrow Rescue of Aging Cardiac Angiogenesis

老化心脏中的血管生成潜力被抑制。初步研究表明，内皮细胞的改变是衰老心脏血管生成活性下降的原因之一。最近的研究还表明，骨髓是内皮前体细胞和其他类型的血管细胞的来源，这些细胞可能有助于调节血管生成活动。因此，作为研究衰老心脏血管生成潜能抑制的一种方法，我们使用骨髓移植作为一种手段来恢复在老年宿主心脏血管生成调节中起关键作用的细胞群。特别是，研究表明，当移植年轻小鼠(3个月大)的骨髓时，衰老小鼠(18个月大)的心脏血管生成潜力有显著改善。这些初步数据有力地支持了这样的假设，即特定的骨髓来源细胞亚群(S)可以恢复衰老的心脏血管生成潜力。该项目的长期目标是利用专门针对特定的骨髓来源细胞亚群(S)的分子和/或细胞方法来增强衰老心脏的血管生成活性，这一亚群在恢复衰老的心脏血管生成活性方面至关重要。结合组织学和蛋白质组学方法，结合骨髓移植到衰老的海洋宿主中，我们将鉴定细胞类型并表征被招募到衰老宿主的心脏血管生成灶中的骨髓来源细胞的表面表位。这些研究的结果将被纳入未来旨在确定介导衰老心脏血管生成潜力恢复的分子和细胞作用的研究中。此外，这些研究将为开发旨在改善老化心脏血管功能的新方法奠定基础。

Angiogenic potential in the aging heart is depressed. Preliminary studies have revealed that alterations in endothelial cells contribute to this decline in senescent cardiac angiogenic activity. Recent studies have also demonstrated that the bone marrow is a source of endothelial precursor cells as well as other vascular cell types that may contribute to the regulation of angiogenic activity. Therefore as one approach to study the depression in senescent cardiac angiogenic potential, we have employed bone marrow transplantation as a means of restoring cell populations that are critical in the regulation of cardiac angiogenesis in the aging host. Specifically, it was shown that when transplanted with the bone marrow of young mice (3 months old), the senescent mice (18 months old) had a marked improvement in their cardiac angiogenic potential. These preliminary data strongly support the hypothesis that a specific subpopulation(s) of bone marrow derived cells can restore senescent cardiac angiogenic potential. The long-range goals of this project are to enhance to angiogenic activity in the aging heart employing molecular and/or cellular approaches specifically directed at the distinct subpopulation(s) of bone marrow- derived cells that are critical in the restoration of senescent cardiac angiogenic activity. Using a combination of histological and proteomic approaches in conjunction with bone marrow transplantation into senescent marine hosts we will identify the cell types and characterize the surface epitopes of the bone marrow derived cells that are recruited to cardiac angiogenic foci in the aging host. The results of these studies will then be incorporated into future studies designed to identify the molecular and cellular actions mediating the restoration of senescent cardiac angiogenic potential. Moreover, these studies will establish a basis for the development of novel approaches directed at improving vascular function in the aging heart.