Biomedical Engineering Reference
In-Depth Information
ventilation-perfusion ratios. Increased resistance of pulmonary arterioles results
from elevated pulmonary arterial smooth myocyte tone as well as hypertrophy and
proliferation. Agent HIF1 decreases the expression of voltage-dependent K
V
1.5 and
K
V
2.1 channels and increases that of transient receptor potential TRPC1 and TRPC6
channels and Na
+
-H
+
exchangers in pulmonary arterial smooth myocytes [
1229
].
Moreover, HIF1 triggers the production of endothelin-1 as well as angiotensin
convertase and angiotensin receptor AT
1
in human pulmonary artery fibroblasts.
10.6.2.9
Histone Deacetylases
Phosphorylated class-2A histone deacetylases recruit 14-3-3 proteins for seques-
tration in the cytoplasm to overcome their repressor activity, because they cannot
interact with their cognate transcription factors and corepressors. Dephosphoryla-
tion of class-2A HDACs allows nuclear import and gene activity repression.
Many kinases and phosphatase could phosphorylate and dephosphorylate
HDAC7 according to location and signaling time for adequate and efficient cell
reponses to stimuli, respectively. Phosphatase PP2 constitutively dephosphorylates
HDAC7 histone deacetylase to control its function as a regulator of T-lymphocyte
apoptosis and endothelial cell functioning during angiogenesis [
1230
].
36
10.6.2.10
Histones
Histone-2A family member H2ax involved in DNA-damage repair promotes sur-
vival and proliferation of endothelial cells during hypoxia and hypoxia-induced
angiogenesis [
1231
]. Hypoxia leads to H2ax phosphorylation (H2ax
P
-H2ax)
in endothelial cells, similarly to H2ax C-terminus phosphorylation that results from
DNA damage by ataxia teleangiectasia mutated kinase (ATMK), ATM- and Rad3-
related kinase (ATRK), and DNA-dependent protein kinase. Hypoxia-triggered
neovascularization requires functional H2ax in endothelial cells.
or
γ
10.6.3
MicroRNAs
Post-transcriptional control of angiogenesis is ensured by microRNAs. MicroRNAs
can be divided into 2 sets: pro- and anti-angiogenic microRNAs. Pro-angiogenic
microRNAs include Let7, miR17-2, miR27b, miR126, miR130a, miR210, miR296,
36
Enzyme HDAC7 is transiently and strongly expressed in CD4
+
,CD8
+
thymocytes, as it
represses a pro-apoptotic gene that encodes nuclear receptor NR4a1 (a.k.a. testicular receptor
TR3, nerve growth factor NGF1b, and Nur77). Enzyme HDAC7 in the vascular endothelium
downregulates MMP10 matrix metallopeptidase.
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