Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 507

preferentially suppresses the expression of connective tissue growth factor.
MicroRNA-19 impedes thrombospondin Tsp1 activity. The miR17-92 cluster is
also involved in the regulation of B-cell differentiation.
MicroRNA-378 improves not only tumor cell growth, but also tumor angiogene-
sis, as it inhibits SuFu and Fus1 tumor suppressors.
Dicer depletion reduces the expression of microRNAs that control the production
of high-mobility group (HMG)-box protein HMGB1 transcriptional suppressor,
which targets NOx organizer NOxO2 of the NADPH oxidase complex. MicroRNAs,
such as miR21, miR126, and miR155, contribute to vascular inflammation [ 933 ].
Overexpression of MiR21 causes neointima formation. MicroRNA-126 inhibits
TNF -stimulated VCAM1 that favors leukocyte adherence to the vascular endothe-

lium. MicroRNA-155 represses the expression of angiotensin-2 AT1R receptor.
MicroRNA-155 expression is induced in macrophages by TNF

α

α and Ifn β for

proliferation of granulocytes and monocytes during inflammation. 70
In normal adult swine, expression of endothelial microRNA-10a is lower in
the inner aortic arch and aorto-renal branches than elsewhere; subsequently those
of HoxA1, a miR10a target, and inflammatory biomarkers CCL2 chemokine,
interleukin-6 and -8, VCAM-1, and E-selectin rises in the same regions [ 934 ].
Transcripts

that encode 2 regulators of I κ B α degradation, MAP3K7 and

β -transducin repeat-containing ubiquitin ligase, contain a miR10a-binding site

in their 3 UTR region. MicroRNA-10a thus prevents activation of NF B and thus

expression of a pro-inflammatory endothelial phenotype in the arterial bed.

κ

9.5.11 Angiogenesis Guidance Molecules

New blood vessels arise from existing ones by emergence of tips with
non-proliferating tip cells that have a guidance role and are followed by
sprouting with proliferating stalk cells. Signaling involved in vessel (and axon)

70 MicroRNA-155 is also required for functioning of B and T lymphocytes, as well as dendritic
cells. Furthermore, miR424 is activated by transcription factor PU.1 to impede translation of
transcription factor NFI-A that hinders M-CSF receptor actvity during monocyte differenti-
ation [ 933 ]. MicroRNA-17-5p-20a-106a also controls monocytopoiesis via AML1 and CSF1
receptor. MicroRNA-146 is elicited in macrophages by pro-inflammatory cytokines via NF κ B.
Myeloid-specific miR223 regulates progenitor proliferation and granulocyte differentiation and
activation during inflammation.