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.
