Vascular Development - Anatomy & Physiology

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Introduction

Blood vessel formation is a combination of the following three processes:

  • Vasculogenesis: the formation of blood vessels from endothelial progenitor cells.
  • Angiogenesis: the sprouting of new capillaries from pre-existing vessels.
  • Arteriogenesis: the remodelling of newly formed or pre-existing vascular channels into larger and more muscular arterioles.

Vasculogenesis

  • Vasculogenesis occurs during the third week of gestation in domestic mammals, initially in the yolk sac and afterwards in the allantois.
  • The blood vessels form from blood islands containing haemangioblasts which develop from mesodermal cells in the presence of fibroblast growth factor.
  • Exposure to angiopoietin and vascular endothelial growth factor (VEGF) stimulate differentiation of haemangioblasts to angioblasts which ultimately develop into endothelial cells.

Angiogenesis

The sprouting of new capillaries from existing blood vessels occurs when surrounding cells become hypoxic. A low partial pressure of oxygen causes an increase in levels of hypoxia-inducible factor (HIF), this in turn stimulates cells to release vascular endothelial growth factor (VEGF) leading to new vessel formation. Other growth factors such as angiopoietin also play an important role. Angiopoietin-1 interacts with the Tie-2 receptor on endothelial cells at the sites where sprouting occurs. Platelet derived growth factor (PDGF) and transforming growth factor-β (TGF-β) influence the maturation of the capillary network. Angiopoietin-2 expression in the absence of VEGF leads to vessel regression and apoptosis.

Arteriogenesis

The volume and pressure of blood flowing in the network dictates the degree of development of individual vessels. The channels which carry blood at high pressure develop additional tissue layers from the surrounding mesoderm thereby becoming thick-walled. The diameter of these vessels also increases and they become known as arteries. Differentiation of mesenchymal cells to smooth muscle is driven by growth factors released from endothelial cells.

Fate of the Aortic Arches

The primitive heart is a simple tube with one inlet and one outlet and empties into embryonic structures called aortic arches. These are organised along the same lines as the blood vessels supplying the gills of fish. Most vertebrate embryos have six aortic arches but in the majority of mammals the fifth arch does not develop. Ultimately, some of the arches are remodelled whereas others atrophy. Not all of the arches are present simultaneously; the first and second develop before the fourth and sixth and by the time the sixth pair of arteries have formed, very little of the first two pairs remains. Major changes to the aortic arches occur between the third and fourth week of gestation in dogs and between the third and seventh week in horses. The first pair of aortic arch arteries atrophy and only remnants of the second pair persist as the stapedial arteries supplying the middle ear. The common, external and internal carotid arteries are all derived from the third aortic arch. The left fourth aortic arch contributes to the arch of the aorta and the right fourth aortic arch forms the proximal region of the right subclavian artery. The development of the sixth aortic arch arteries is complex with the proximal section of the left arch forming the proximal part of the left pulmonary artery and the distal region fashioning the ductus arteriosus. The proximal section of the right sixth aortic artery persists as the proximal region of the right pulmonary artery and the distal part atrophies.


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