4.6 Review

Vascular endothelial cell specification in health and disease

Journal

ANGIOGENESIS
Volume 24, Issue 2, Pages 213-236

Publisher

SPRINGER
DOI: 10.1007/s10456-021-09785-7

Keywords

Endothelial cell specification; Blood vessel development; Lymphatic vessel development; Arterial-venous malformations; Lymphatic malformations

Funding

  1. NIH [R01 HL146056, R01 DK118728, U2EB017103, T32 HL007284]

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There are two vascular networks in mammals which play integral roles in the body's supply and drainage systems. These networks consist of arteries, veins, capillaries, and lymphatic vessels with specialized functions. Endothelial cells, the main components of these vessels, have specific identities that contribute to their physiological functions and responses to circulating factors. Dysregulation of these processes can lead to vascular malformations, and various therapeutic approaches have been developed for their treatment.
There are two vascular networks in mammals that coordinately function as the main supply and drainage systems of the body. The blood vasculature carries oxygen, nutrients, circulating cells, and soluble factors to and from every tissue. The lymphatic vasculature maintains interstitial fluid homeostasis, transports hematopoietic cells for immune surveillance, and absorbs fat from the gastrointestinal tract. These vascular systems consist of highly organized networks of specialized vessels including arteries, veins, capillaries, and lymphatic vessels that exhibit different structures and cellular composition enabling distinct functions. All vessels are composed of an inner layer of endothelial cells that are in direct contact with the circulating fluid; therefore, they are the first responders to circulating factors. However, endothelial cells are not homogenous; rather, they are a heterogenous population of specialized cells perfectly designed for the physiological demands of the vessel they constitute. This review provides an overview of the current knowledge of the specification of arterial, venous, capillary, and lymphatic endothelial cell identities during vascular development. We also discuss how the dysregulation of these processes can lead to vascular malformations, and therapeutic approaches that have been developed for their treatment.

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