Endogenous Regulators of Plaque Angiogenesis

斑块血管生成的内源性调节剂

• 批准号: 6612865
• 负责人: KAREN Simpson MOULTON
• 金额: $ 30.12万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6612865
• 关键词: angiogenesis; angiogenesis factor; angiogenesis inhibitors; apolipoprotein E; atherosclerotic plaque; cell proliferation; inflammation; laboratory mouse; low density lipoprotein receptor; vascular endothelial growth factors; vascular endothelium

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.

描述（申请人的摘要）：人类和其他人的动脉粥样硬化病变 该疾病的动物模型与VASA增加的区域有关 浮游生物增殖并延伸到内膜层。已发布数据 建议这些斑块毛细血管可能是细胞增殖的标志物，促进 炎症细胞进入病变，或可能参与斑块出血 可能会引发心肌梗塞或中风的破裂。最近 研究，内皮细胞抑制剂减少了内膜新生血管形成和 APOE缺陷小鼠的斑块生长，这表明斑块血管生成 有助于动脉粥样硬化的进展。由于它与 疾病进展和急性缺血并发症的发展，这是 与了解机制并确定内源性因素有关 调节斑块血管生成。 内膜新血管形成已记录在ApoE的晚期病变中 - / - 老鼠。动脉粥样硬化病变将在无血清的体外测定中进行测试 斑块引起的发芽形成以表征相对生物学 刺激病变中血管生成的活性。 apoe - / - 小鼠将被治疗 这些内源性因素的特定拮抗剂可以确定它们是否 调节体内斑块血管生成和病变的生长。内接an 血管生成的内源性抑制剂保留在内侧 主动脉。 APOE - / - 小鼠将与缺乏胶原蛋白的小鼠交叉 xvlll/endostatjn确定是否失去了内源性抑制剂的损失 主动脉中的血管生成将增强内膜新血管和斑块 生长。用不同的血管生成抑制剂处理的动脉粥样硬化病变 将评估以确定这些药物对 病变的细胞含量和营业额。