Biomedical Engineering Reference
In-Depth Information
P21-activated kinase-1.
26
Glutamate carboxypeptidase-2 thus participates in an
autoregulatory loop.
10.5.8
Collagen Prolyl 4-Hydroxylase
Transcription factor P53 activates the gene that encodes collagen prolyl
4-hydroxylase. The latter is required for extracellular release of collagen-derived
peptides, such as endostatin and tumstatin that inhibit angiogenesis [
1206
].
10.6
Mediators of Vascular Formation
The formation of new blood vessels, the patterning of the ramified network,
27
as well as the remodeling of existing blood vessels require the migration and
proliferation of various cell types controlled by manifold substances, such as
guidance and growth factors, and their inhibitors (Table
10.11
). Microvascular
growth and remodeling, which is influenced by the mechanical factors (local stress
field), are variable. These phenomena are indeed based on sprouting, non-sprouting
(intussusceptive), and mixed angiogenesis.
10.6.1
Navigation Signals
Angiogenesis is conducted by an initiation and patterning program. Guidance
molecules regulate patterning of blood vasculature. The navigation of migrating
angiogenic components requires guidance signaling via ligand-receptor complexes,
such as: (1) ephrins with EPH receptors; (2) Slit ligands with Roundabout (Robo)
receptors; (3) semaphorins with plexin and neuropilin receptors; and (4) netrins
with plasmalemmal receptors Deleted in colorectal carcinoma (DCC), DCC-related
neogenin (Ngn), and uncoordinated-5 (Unc5) receptors [
1207
,
1208
].
28
26
Inhibition of P21-activated kinase-1 enhances the association of glutamate carboxypeptidase-2
with filamin-A.
27
The vascular network is locally composed of arteriolar branched and venular junctional networks
interconnected by the capillary bed. These arteriolar and venular networks are afferent to and
efferent from irrigated tissues, or efferent from and afferent to the heart pump, respectively. As the
heart can be defined as the center of circulating blood circuitry, the latter meaning is preferable.
28
The ephrin-B2-EPHb4 signaling is involved in arteriovenous differentiation. Four Slit receptors
exist, the Roundabouts (Robo). Receptor Robo4 and plexin-D1 are expressed by endothelium.
Semaphorin-3 inhibits endothelial cell motility via plexin-D1. Neuropilins, in competition with
Sema3a, associate with VEGF receptors and allow binding of heavy VEGF isoforms to endothelial
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