"Intravascular Flow Field Regulation of Intussusceptive Angiogenesis"

“肠套叠血管生成的血管内流场调节”

• 批准号: 7749825
• 负责人: Grace Seungyeon Lee
• 金额: $ 4.82万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-06-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7749825
• 关键词: Adult; Atherosclerosis; Attention; Biological Assay; Blood Circulation; Blood Vessels; Blood capillaries; Blood flow; Caliber; Cancer Biology; Colitis; Data; Development; Diabetes Mellitus; Dose; Endothelial Cells; Foundations; Gene Expression; Generations; Goals; Hematoporphyrin Derivative; Hypertension; Intussusception; Laboratories; Lasers; Light; Limb structure; Mechanical Stress; Membrane; Methods; Microscopy; Morphogenesis; Names; Natural regeneration; Pathologic Processes; Pathology; Patients; Photochemotherapy; Photosensitizing Agents; Physiological; Play; Process; Reactive Oxygen Species; Refractory; Regulation; Research; Role; Simulate; Site; Structure; Testing; Therapeutic; Three-Dimensional Imaging; Tissue Engineering; Tissues; United States National Institutes of Health; Wound Healing; angiogenesis; capillary; chorioallantoic membrane; combat; in vivo; membrane model; programs; response; tumor

DESCRIPTION (provided by applicant): Two distinct forms of angiogenesis have been documented: sprouting and intussusception. While mechanisms of sprouting angiogenesis have received considerable attention, especially in the context of tumor therapy, relatively little study has been devoted to understanding intussusceptive angiogenesis. In intussusceptive angiogenesis, the capillary wall extends into the lumen to split a single vessel in two. A pillar or a tissue column found near vessel bifurcations indicates the zone of luminal contact. Recent data from our laboratory, as well as others, have demonstrated that intussusceptive angiogenesis is a mechanism for the rapid expansion of existing microvascular networks. The finding suggests this mechanism plays a widely implicated role in various physiologic and pathologic processes. A better understanding of the mechanism will undoubtedly aid in the NIH initiatives in cancer biology as well as wound healing and tissue-engineering. Our hypothesis is that the process of intussusceptive angiogenesis is regulated by intravascular flow fields, i.e. the volume and symmetry of intravascular blood flow. The specific aims are to: 1) assess the effect of increased or decreased volumetric flow to a vessel bifurcation with an intussusceptive pillar and 2) to analyze symmetric or asymmetric flow fields at a vessel bifurcation with an intussusceptive pillar. The proposed research will be carried out in the chick chorioallantoic membrane (CAM) model, a well- established in vivo angiogenesis assay. Photodynamic therapy (PDT) is the chosen method for the dynamic manipulation of the CAM vessels. After a systemic administration of photosensitizer, a laser or a focused light dose given at the specific wavelength produces rapid, local, highly precise vessel occlusion. The subsequent changes in the vessel with intraluminal pillar will be followed using intra-vital microscopy and confirmed by vascular casting and 3D imaging According to the Angiogenesis Foundation, at least 184 million patients in Western nations could benefit from some form of anti-angiogenic therapy, and almost twice the number of patients would benefit from some form of pro-angiogenic therapy. A comprehensive understanding of the multi-modal process such as angiogenesis is crucial not only in development of new therapy but also in combating pathologies refractory to current therapy.

描述（由申请人提供）：两种不同形式的血管生成已被记录：发芽和肠套叠。虽然发芽血管生成的机制受到了相当大的关注，特别是在肿瘤治疗的背景下，但对肠套敏感血管生成的研究相对较少。在肠套激血管生成中，毛细血管壁延伸至管腔，将单个血管一分为二。在血管分叉附近发现的柱或组织柱表示管腔接触区。来自我们实验室以及其他实验室的最新数据表明，肠套敏感血管生成是现有微血管网络快速扩张的一种机制。这一发现表明，这一机制在各种生理和病理过程中起着广泛的作用。对这一机制的更好理解无疑将有助于美国国立卫生研究院在癌症生物学、伤口愈合和组织工程方面的研究。我们的假设是，肠套激血管生成的过程是由血管内流场调节的，即血管内血流的体积和对称性。具体目的是：1)评估容积流量增加或减少对肠套管柱血管分岔的影响；2)分析肠套管柱血管分岔处对称或不对称流场。拟议的研究将在鸡绒毛膜尿囊膜（CAM）模型中进行，这是一种成熟的体内血管生成实验。光动力疗法（PDT）是CAM血管动态操作的首选方法。在系统使用光敏剂后，特定波长的激光或聚焦光剂量会产生快速、局部、高度精确的血管闭塞。根据血管生成基金会的数据，在西方国家，至少有1.84亿患者可以从某种形式的抗血管生成治疗中受益，几乎两倍的患者可以从某种形式的促血管生成治疗中受益。对血管生成等多模式过程的全面理解不仅对新疗法的发展至关重要，而且对对抗当前疗法难以治愈的病理也至关重要。