Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 411

Tabl e 8. 9. Control of phenotype of vascular smooth myocytes (Source: [ 745 ]). The synthetic,
proliferative phenotype can result from increases in angiotensin-2, intracellular Ca 2 + level, or
stretch. On the other hand, the serum response factor (SRF)-myocardin complex maintains the
contractile state. Cell contractility is associated with Ca 2 + ion and RhoA signaling. Signaling
initiated by Wnt and MAPK determines cell shape and promotes cell differentiation. Elongation of
smooth myocytes supports the contractile phenotype.

Controllers Mediators

PDGF KLF4, ELk1

TGF β KLF4, ELk1

Notch HERP1

Wnt MAPK

Stretch RhoA

Calcium channels Calcium

Angiotensin-2 RhoA

The canonical Wnt pathway is controlled by Dickkopf inhibitors that pre-
clude Wnt-LRP interaction. Both canonical and non-canonical Wnt pathways are
inhibited by secreted Frizzled-related proteins and Wnt inhibitory factor-1 that
prevent Wnt-Fz linkage. Nevertheless, Dickkopf-1 promotes SMC proliferation in
rat mesenteric microvasculature [ 753 ].
Differentiation of venous and arterial smooth myocytes may also be regulated
by Wnt proteins. Wnt3a promotes the expression of the early myofibroblast
marker SM22

; Wnt7b may intervene during differentiation of pulmonary smooth
myocytes [ 753 ].

α

8.5.3.5 Proliferation of Vascular Smooth Myocytes

MicroRNAs contribute to the regulation of vascular smooth myocyte fate. The mi-
croRNA cluster miR143-miR145 as well as miR21 and miR1 support the contractile
phenotype. On the other hand, miR221, miR146a, miR26a, and miR24 promote
cell proliferation after vascular injury [ 745 ]. The microRNA cluster miR143-
miR145 may be activated by Jagged-1-Notch and myocardin-SRF axes. In young
hypertensive patients, the expression of angiotensin AT 1 receptor is negatively
correlated with miR155 agent.
Kr upple-like factors KLF4 and KLF5, ETS-like transcription factor ELk1, HES-
related repressor protein HERP1, FoxO4, and RelA subunit of NF B hinder

vSMC-specific gene expression. These mediators propagate effects of PDGFbb,
TGF

κ

, and Notch, at least partly by disrupting SRF-myocardin interaction, thereby
supporting the synthetic and proliferative phenotype of vascular smooth myocytes
(Table 8.9 )[ 745 ]. MicroRNA-143 and -145 are targets of SRF and myocardin,
which maintain the contractile phenotype of vascular smooth myocytes and target
KLF4 and ELk1 transcription factors.

β