POSTNATAL VASCULOGENESIS IN CARDIOVASCULAR DISEASE

心血管疾病中的产后血管发生

• 批准号: 6030922
• 负责人: Jeffrey Isner
• 金额: $ 34.81万
• 依托单位: STEWARD ST. ELIZABETH'S MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6030922
• 关键词: CD34 molecule; angiogenesis; beta galactosidase; blood vessels; bone marrow; bone marrow transplantation; cell differentiation; cell growth regulation; cell migration; cell proliferation; enzyme mechanism; gene expression; genetically modified animals; laboratory mouse; laboratory rabbit; nonsurgical revascularization

DESCRIPTION (Adapted from Investigator's Abstract): Postnatal neovascularization has been previously considered to result exclusively from the proliferation, migration, and remodeling of fully differentiated endothelial cells (ECs) derived from pre-existing blood vessels, i.e., angiogenesis. The formation of blood vessels from endothelial progenitor cells (EPCs)- i.e., vasculogenesis- has been considered restricted to embryogenesis. Preliminary studies recently completed in the investigator's laboratory suggest that under appropriate conditions, a subpopulation of CD34+ and/or Flk-1+ cells circulating in the peripheral blood can differentiate into ECs in vitro. Moreover, the investigators observed that such endothelial progenitor cells could incorporate into foci of ongoing neovascularization in rabbit and murine models of limb ischemia. When normal mice were lethally irradiated and transplanted with bone marrow (BM) harvested from transgenic mice, constitutively over- expression beta-galactosidase )beta-gal), the investigators observed incorporation of beta-gal-expressing BM-derived EPCs into foci of neovascularization in murine models of corneal injury, hind limb ischemia, myocardial infarction, and syngeneic colon cancer. These same models may be utilized to demonstrate that enhancement of circulating EPCs by exogenous administration or endogenous mobilization of EPCs may augment neovascularization. Preliminary data of the investigator thus challenge the conventional notion that postnatal vascularization is synonymous with angiogenesis. The experiments outlined in the proposal are designed to establish further evidence in this regard, clarify certain mechanisms and circumstance which may be responsible for modulating the contribution of vasculogenesis to postnatal neovascularization, and explore the possibility that modulation of vasculogenesis might be used therapeutically to augment as well as to inhibit neovascularization.

描述（根据调查员的摘要改编）：产后 先前认为新血管化仅导致 完全分化的扩散，迁移和重塑 源自先前存在的血管的内皮细胞（EC），即 血管生成。从内皮祖细胞形成血管 细胞（EPC） - 即血管发生 - 被认为仅限于 胚胎发生。初步研究最近完成了 研究者的实验室建议，在适当的条件下， 在周围循环的CD34+和/或FLK-1+细胞的亚群 血液可以在体外分化为EC。而且，调查人员 观察到这种内皮祖细胞可以纳入 兔子和肢体鼠模型中持续的新血管形成的焦点 缺血。当正常小鼠被致命照射并用 从转基因小鼠收获的骨髓（BM），组成性地过度 表达β-半乳糖苷酶）β-gal），研究者观察到 将表达β-GAL的BM衍生的EPC纳入焦点 角膜损伤的鼠模型，后肢缺血，新生血管化， 心肌梗死和同性结肠癌。这些模型可能 被用来证明通过 EPC的外源给药或内源动员可能会增加 新血管形成。因此，研究者的初步数据挑战 传统观念是产后血管化是与 血管生成。该提案中概述的实验旨在 在这方面建立进一步的证据，澄清某些机制和 可能导致调节贡献的情况 血管生成到产后新血管形成，并探索 可以使用调节血管发生的可能性 治疗以增加并抑制新血管形成。