Development

How does the vascular system form?

What is vasculogenesis?

Vasculogenesis refers to the morphogenetic process occurring during the earliest stages of embryonic development by which a de novo vascular system, consisting of the heart and the blood vessels, is formed from mesodermal precursor cells.

Vasculogenesis mainly involves the formation of a primary vascular plexus. This is initiated when mesodermal precursor cells are induced to differentiate into angioblasts and hematopoietic cells by growth factors, mainly those belonging to the vascular endothelial growth factors (VEGF) subfamily [1] [2][3]. The angioblastic and hematopoietic cell lineages are known to derive from a common intermediary precursor called the hemangioblast [4]. The angioblasts further differentiate into endothelial cells, which then come together to form the nascent blood vessels; while some angioblasts form blood vessels at the site of their origin, others may migrate to distant locations to form vascular networks at these new sites [5].

What is angiogenesis?

Soon after the primary vascular plexus is formed in early embryos, new blood vessels start forming from existing ones during subsequent stages of embryonic development, in a process called angiogenesis. This physiological process also occurs in adult life during vascular tissue regeneration, wound healing mechanisms, as well as in a number of pathogenesis conditions such as cancers, cardiovascular, rheumatic and ophthalmic diseases [6] [7]. Angiogenesis takes place through one of these two mechanisms: sprouting from or splitting of already existing blood vessels. During sprouting angiogenesis, new capillaries branch off from existing blood vessels as endothelial cells migrate in response to chemotactic factors such as VEGF, and proliferate into endothelial clusters. This is followed by the formation of a lumen, which results in a functionally mature endothelium. For instance, the sprouting of neural capillaries in response to VEGF secreted in the neural tube periventricular regions is a classic case of sprouting angiogenesis during embryogenesis [8]. The alternate, non-sprouting mechanism of angiogenesis (also known as intussusceptive angiogenesis) involves the septation of existing vessels by the extracellular matrix, and is mainly observed during the vascularization of lungs during development [9][10].

The blood vessels formed during vasculogenesis and angiogenesis undergo further ‘pruning’ (elimination of some endothelial cells) and remodeling in order to evolve into a functionally mature vascular system. This process is responsible for giving rise to vessels with different sizes and flow patterns. Once blood circulation starts within these blood vessels, the vascular system gets shaped further by hemodynamic forces arising from the blood flow. For instance, shear stress generated by blood flow is known to alter endothelial cell shape and dynamics by stimulating PGDF signaling and also by inducing the formation of endothelial stress fibers [11][12].

References

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9. Ackermann M, Houdek JP, Gibney BC, Ysasi A, Wagner W, Belle J, Schittny JC, Enzmann F, Tsuda A, Mentzer SJ, and Konerding MA. Sprouting and intussusceptive angiogenesis in postpneumonectomy lung growth: mechanisms of alveolar neovascularization. Angiogenesis 2013; 17(3):541-51. [PMID: 24150281]
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