Biomedical Engineering Reference
In-Depth Information
lymphatic defects encompass chylothorax, hyperplasia of collecting lymphatic
vessels, agenesis of valves, and abnormal recruitment of smooth myocytes into
lymphatic capillaries [
1371
]. Moreover, specific ablation of ephrin-B2 on vascular
smooth myocytes provokes their migration to cover lymphatics [
1372
]. Tissue-
specific mutant mice display perinatal lethality with vascular defects in lung, kidney
glomeruli, digestive tract, and skin. Receptor EPHb4 is expressed in collecting
lymphatic vessels and lymphatic capillaries, while ephrin-B2 is only expressed in
collecting lymphatic vessels in adults.
10.8.3
Other Mediators
Cytosolic protein Tyr kinase spleen tyrosine kinase (SYK) and adaptor lym-
phocyte cytosolic protein LCP2 control the separation of lymphatic and blood
vessels [
1184
]. Both limit the number of lymphaticovenous anastomoses.
Podoplanin, a transmembrane glycoprotein highly expressed in glomerular
podocytes and lymphatic endothelial cells, may intervene in lymphatic patterning.
Integrin-
α
9
β
1
, a receptor for vascular endothelial cell adhesion molecule-1,
tenascin-C, and osteopontin, is highly expressed in lymphatic endothelial cells.
Once bound to fibronectin,
β
1
-integrin interacts with VEGFR3 and can induce its
phosphorylation to modulate cell migration, proliferation, and survival. Integrin-
α
9
β
1
binds VEGFc and VEGFd subtypes.
10.9
Modeling of Angiogenesis
Angiogenesis is a interconnected set of events occurring in sequence and in
parallel, on multiple levels, triggered by a major stimulus, hypoxia. In response
to hypoxia, the transcription factor hypoxia-inducible factor HIF1 activates trans-
crition of numerous genes, especially vascular endothelial growth factor (VEGF).
Therefore, the 2 prominent chemicals of angiogenesis models are O
2
trigger and
VEGF messenger. The latter stimulate chemotaxis and proliferation in endothelial
cells during sprouting, the main investigated process. Angiogenesis is modeled
at different length scales, from molecule (eventually cell signaling cascades) to
cells (proliferation and migration) and tissue (molecular transfer and microvascular
network).
Models are mainly based on partial differential equations with spatially dis-
tributed variables and appropriate boundary conditions. The predominant strategy
relies on transport-reaction differential equations based on the continuum concept.
However, hybrid approaches are explored, in addition to discrete models and
ordinary differential equations [
1373
].
Blood flow can be computed in a 3D geometrical model of a microvascular
network; convection-diffusion-reaction partial differential equations governing
Search WWH ::
Custom Search