Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 643

10.6.6 Hormones and Cytokines

Small hormones, such as prolactin, growth hormone, and placental lactogen,
secreted by endothelia, promote angiogenesis. 63 Their cytokine receptors that
belong to class-1 family activate the JaK-STAT pathway. However, proteolytic
fragments of these small hormones that result from cleavage by extracellular
metallopeptidases of the bone morphogenetic protein BMP1 subgroup have anti-
angiogenic effects [ 1284 ]. 64
Interleukin-20 65 stimulates both macro- and microvascular endothelial cells via
activation of IL20R1-IL20R2 or IL22R1-IL20R2 receptors and various signaling
effectors, such as JAK2-STAT5, ERK1, ERK2, PKB, Rac and Rho GTPases, NO,
and Ca 2 + [ 1285 ]. In particular, IL20 activates NOS3 that can then move away
from the plasma membrane. Synthesis of NO occurs mostly near the cortical and
perinuclear region. Both activated PKB that phosphorylates NOS3 and rapid, strong
Ca 2 + influx favor NO synthesis. Interleukin-20 promotes vessel maturation and
remodeling, but not endothelial cell proliferation and motility. Delivery of IL20 to
ischemic muscles in a rat hind-limb model improves arteriogenesis.

10.6.6.1 Angiopoietins

Two main isoforms of angiopoietins — Ang1 and Ang2 — bind endothelial cell-
specific Tyr kinase with domains TIE2 (Fig. 10.3 ). 66 Isoforms angiopoietin-3
and -4 are human and mouse orthologs that exert a negative or positive effect in
angiogenesis according to the context.

63 Prolactin operates in reproduction, growth, metabolism, immunity, osmoregulation, and behav-
ior. Growth hormone not only stimulates growth, but also modulates metabolism, reproduction,
and immunity, among other activities. Placental lactogen acts on mammary development, corpus
luteum maintenance, and progesterone production.
64 The bone morphogenetic protein BMP1 family comprises structurally similar metallopeptidases:
BMP1, mammalian Tolloid, and mammalian Tolloid-like Tll1 and Tll2. BMP1-like peptidases
participate in the formation of the extracellular matrix by processing precursors: procollagens-1,
-3, -5, -7, and -11 into functional ECM components; prolysyl oxidase zymogen into enzyme that
catalyzes crosslinks in collagens and elastins; prolaminin-5; precursors of proteoglycans biglycan
and osteoglycin; etc. BMP1-like peptidases activate certain TGF β complexes, including BMP2,

BMP4, GDF8, GDF11, and TGF 1.

65 Interleukin-20 belongs to the IL10 family with IL10, IL19, IL22, IL24, and IL26. Many cell
types produce IL20, such as monocytes and epithelial and endothelial cells.
66 The endothelial receptor protein Tyr kinase with Ig and EGF homology TIE2 is also termed Tyr-
protein endothelial kinase TEK. Receptor TIE1 may build TIE1-TIE2 heterodimers to contribute
to TIE2 signal transduction. Besides, Ang1-TIE2 signaling operates in the maintenance of
hematopoietic stem cells.

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