Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 664

(valine-to-glutamate transition [V600E]), suppression of bRaf signaling switches
off the ERK pathway and inhibits the synthesis of pro-angiogens needed for the
growth, maintenance, and spread of solid tumors [ 1358 ].

10.8 Lymphangiogenesis

The lymphatic vascular system participates in the maintenance of tissue fluid
balance, traveling of immunocytes, and resorption of dietary lipids in the gut (i.e.,
penetration in the blood circulation and transfer after absorption and crossing of the
intestinal barrier). In body's tissues, Lymphatic vessels return interstitial fluid and
proteins to the blood stream.
Lymph vessels form an unidirectional vasculature of close-ended terminal
lymphatics that drain through a network of collecting lymphatics, lymph nodes,
lymphatic trunks and ducts into the venous circulation. The mature lymphatic
system consists of the lymphatic vasculature and lymphoid organs (lymph nodes,
Peyer's patches, tonsils, spleen and thymus). The lymphatic vasculature resides
in most of the body domains, except central nervous system, cartilage, epidermis,
cornea, and retina.
Close-ended lymphatic capillaries do not have basement membranes and are not
covered by smooth myocytes, but are tethered by anchoring filaments to collagen
fibers of the extracellular matrix. As the surrounding interstitial pressure changes,
these anchoring filaments extend or colapse, causing lymphatic capillaries dilation
or constriction to propel lymph, respectively.
Lymphatic capillaries merge in precollecting lymphatics, themselves in larger
secondary collecting and collecting lymphatics. Large collecting lymphatics are
covered by smooth myocytes that contract to assist lymph flow. Collecting lym-
phatics contain bileaflet valves. Lymph is drained through the thoracic duct and
right lymphatic duct into the blood circulation via left and right subclavian veins,
respectively.
Lymphatic vessel walls are coated by lymphatic endothelial cells that are inter-
connected by tight and adherens junctions. Lymphatic endothelial cells differentiate
under a proper transcriptional control from veins. Lymphatic vessels form an
independent vascular tree with only few connections to the venous circulation.
Therefore, lymphatic vessels form when the blood vasculature is already func-
tional. According to the current theory proposed by F. Sabin in 1902, the first
lymphatic endothelial cells sprout from embryonic venous endothelial cells and mi-
grate to form the primary lymphatic sacs [ 1359 ]. Circulating endothelial progenitor
cells may contribute to lymphangiogenesis.
The primary lymph sacs and the primary lymphatic plexus appear in 6- to 7-
week-old human embryos. Peripheral lymphatic vessels then form by sprouting
from lymph sacs. Large collecting lymphatic vessels mature by deposition of
a basement membrane, accumulation of mural cells, and formation of valves.
Therefore, lymphangiogenic tissues arise by sprouting, branching, and remodeling.