Endogenous Regulators of Plaque Angiogenesis

描述（申请人摘要）：人类和其他 该疾病的动物模型与血管增加的区域相关。 增殖并延伸到内膜层。公布数据 提示这些斑块毛细血管可能是细胞增殖的标志， 炎症细胞进入病变，或可能参与斑块出血 破裂可能引发心肌梗塞或中风。近几 研究表明，内皮细胞抑制剂减少了内膜新生血管形成， ApoE缺陷小鼠中的斑块生长，这表明斑块血管生成 导致动脉粥样硬化的发展。由于其与 疾病进展和急性缺血性并发症的发展， 与了解机制和确定内生因素有关 调节斑块血管生成。 在ApoE-/-的晚期病变中记录了内膜新生血管形成 小鼠将在无血清体外试验中检测动脉粥样硬化病变， 噬菌斑诱导的芽形成，以表征相关生物 刺激病变血管生成的活性。将对ApoE-/-小鼠进行处理 这些内源性因子的特异性拮抗剂，以确定它们是否 调节体内斑块血管生成和病变生长。内皮抑素 血管生成的内源性抑制剂保留在中间层的 主动脉ApoE-/-小鼠将与缺乏胶原蛋白的小鼠杂交 XVIII/内皮抑制素，以确定内源性内皮抑制素的损失是否 主动脉中的血管生成将增强内膜新血管形成和斑块 增长用不同血管生成抑制剂治疗的动脉粥样硬化病变 将进行评估，以确定这些代理人的功能后果 病变的细胞含量和周转。

DESCRIPTION (Applicant's abstract): Atherosclerotic lesions in humans and other animal models of the disease are associated with areas of increased vasa vasasorum that proliferate and extend into the intimal layer. Published data suggests these plaque capillaries may be markers of cell proliferation, promote inflammatory cell entry into lesions, or may be involved in plaque hemorrhage and rupture that can initiate a myocardial infarction or stroke. In recent studies, endotheljal cell inhibitors reduced intimal neovascularization and plaque growth in ApoE-deficient mice, which suggest plaque angiogenesis contributes to the progression of atherosclerosis. Due to its association with disease progression and the development of acute ischemic complications, it is relevant to understand the mechanisms and to identify the endogenous factors that regulate plaque angiogenesis. Intimal neovascularization has been documented in advanced lesions of ApoE-/- mice. Atherosclerotic lesions will be tested in a serum-free in vitro assay of plaque-induced sprout formation to characterize the relative biologic activities that stimulate angiogenesis in lesions. ApoE-/- mice will be treated with specific antagonists of these endogenous factors to determine if they regulate plaque angiogenesis and lesion growth in vivo. Endostatin an endogenous inhibitor of angiogenesis is retained in the medial layer of the aorta. ApoE-/- mice will be crossed with mice deficient in collagen XVlll/endostatjn to determine if loss of an endogenous inhibitor of angiogenesis in the aorta will enhance intimal neovascularization and plaque growth. Atherosclerotic lesions treated with different angiogenesis inhibitors will be evaluated to determine the functional consequences of these agents on the cell content and turnover of lesions.