page_title: Vascular remodelling in the embryo
section_title: Application to study of disease progression
hierarchical_section_title: Vascular remodelling in the embryo / Application to study of disease progression
caption_attribution_description: English: Neuropilin-2 (Nrp2) expression in normal breast and breast carcinoma tissue. (A) Nrp2 staining was observed in blood or lymph vessels. There was no staining in normal breast epithelium. (×100). (B) In cancer tissue, staining of the Nrp2 protein was identified not only in the vascular endothelial cells, but also in the cytoplasm of cancer cells. Almost all invasive cells were immunopositive for Nrp2. (×200). (C-D) Co-localized expression of Nrp2 (C) and CXCR4 (D) using serial sections of breast carcinoma tissue. (×100). Yasuoka et al. BMC Cancer 2009 9:220 doi:10.1186/1471-2407-9-220
context_page_description: Vascular remodelling is a process which begins usually at day 22, and continues to around the tenth week of human embryogenesis, when, on day 22, an immature heart begins contracting, pushing fluid through the early vasculature. This first passage of fluid initiates a signal cascade and cell movement based on physical cues including shear stress and circumferential stress, which is necessary for the remodelling of the vascular network, arterial-venous identity, angiogenesis, and the regulation of genes through mechanotransduction. This embryonic process is necessary for the future stability of the mature vascular network.
  Vasculogenesis is the initial establishment of the components of the blood vessel network, or vascular tree. This is dictated by genetic factors and has no inherent function other than to lay down the preliminary outline of the circulatory system. Once fluid flow begins, biomechanical and hemodynamic inputs are applied to the system set up by vasculogenesis, and the active remodelling process can begin.
context_section_description: Vascular remodelling in non-embryonic tissues is considered to be symptomatic of disease progression. Cardiovascular disease remains one of the most common causes of death globally and is often associated with the blockage or stenosis of blood vessels, which can have dramatic biomechanical effects. In acute and chronic remodelling, the increase in shear stress due to the decreased diameter of a blocked vessel can cause vasodilation, thereby restoring typical shear stress levels. However, dilation also leads to increased blood flow through the vessel, which can result in hyperaemia, affect physiological regulatory actions downstream of the afflicted vessel, and place increased pressure on atherosclerotic plaques which may lead to rupture. Blockage of blood vessels is currently treated by surgically inserting stents to force vessel diameters open and restore normal blood flow. By understanding the implication of increased shear stress on homeostatic regulators, alternative, less-invasive methods may be developed to treat vessel blockage.
  The growth of tumours often results in reactivation of blood vessel growth and vascular remodelling in order to perfuse the new tissue with blood and sustain its proliferation. Tumour growth has been shown to be self-organizing and to behave more similarly to embryonic tissues than to adult tissues. As well, vessel growth and flow dynamics in tumours are thought to recapitulate the vessel growth in developing embryos. In this sense, embryonic vascular remodelling can be considered a model of the same pathways which are activated in tumour growth, and increased understanding of these pathways can lead to novel therapeutics which may inhibit tumour formation.
  Conversely, angiogenesis and vascular remodelling is an important aspect of wound healing and the long-term stability of tissue grafts. When blood flow is disrupted, angiogenesis provides sprouting vessels which migrate into deprived tissues and restore perfusion. Thus, the study of vascular remodelling may also provide important insight into the development of new techniques to improve wound healing and benefit the integration of tissues from transplants by lowering the incidence of rejection.
caption: Neuropilin 2 expression in (A) blood vessels, (B) carcinoma tissue, (C and D) breast carcinoma tissue with co-localized staining for neuropilin 2 and CXCR4, a chemokine receptor. Neuropilin 2 is a known marker for venous blood vessels, indicating the vascularization of the tumour.[21]
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