Contrast-enhanced Ultrasound Assessment of Angiogenesis

描述(由申请人提供)：正在开发促进血管生成的新策略来治疗慢性冠状动脉疾病或外周血管疾病患者，这些患者不能接受血管重建。这项建议的总体目的是应用新的对比增强超声技术来非侵入性地评估被认为有助于血管生成的分子和细胞过程。超声造影已被用于无创性地评估缺血性心脏和肢体疾病的微血管血流灌注，并可以提供不同血管间的血流和血流量信息。针对α-v整合素或激活白细胞的新型微泡造影剂已经被开发出来，以非侵入性的方式成像整合素的表达和炎症。第一个目标是应用这些技术在空间和时间上表征不同血管生成模型中α-v整合素表达、细胞炎症反应和灌流之间的关系。首先，我们将在小鼠血管生成的Matrigel模型中研究这些事件。其次，我们将在一个内源性血管生成模型中研究α-v整合素的表达、炎症和灌流之间的关系，该模型发生在大鼠严重外周血管疾病引起的缺血反应中。这项建议的第二个目的是确定在大鼠严重外周血管疾病的背景下，使用成纤维细胞生长因子-2进行促血管生成治疗如何影响α-v整合素的表达和炎症模式。这些研究的成功完成将提供可能对开发新的促血管生成策略很重要的信息。这些研究还将验证靶向声学造影在非侵入性评估新的促血管生成治疗和指导患者使用方面的潜在用途。

DESCRIPTION (provided by applicant): Novel strategies for promoting angiogenesis are being developed to treat patients with chronic coronary artery disease or peripheral vascular disease who are not amenable to revascularization. The overall purpose of this proposal is to apply novel contrast-enhanced ultrasound techniques to non-invasively assess molecular and cellular processes that are thought to contribute to angiogenesis. Contrast-enhanced ultrasound has been used to non-invasively assess microvascular perfusion in ischemic heart and limb disease, and can provide information on blood flow and blood volume in the different vascular compartments. Novel microbubble contrast agents targeted to either alpha-v integrins or to activate leukocytes have been developed to non-invasively image integrin expression and inflammation. The first aim will be to apply these techniques to spatially and temporally characterize the relation between alpha-v integrin expression, the cellular inflammatory response, and perfusion in different models of angiogenesis. First, we will study these events in a matrigel model of angiogenesis in mice. Second, we will study the relation between alpha-v integrin expression, inflammation, and perfusion in a model of endogenous angiogenesis that occurs in response to ischemia produced by severe peripheral vascular disease in rats. The second aim of this proposal is to determine how patterns of alpha-v integrin expression and inflammation are influenced by pro-angiogenic therapy with FGF-2 in the setting of severe peripheral vascular disease in rats. Successful completion of these studies will provide information that will likely be important for developing new proangiogenic strategies. These studies will also validate the potential use of targeted contrast ultrasound for non-invasively evaluating new pro-angiogenic treatments and for guiding their use in patients.