Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 421

MicroRNAs can regulate the differentiation of multipotent stem cells into a
specific lineage as well as reprogramming of cells. MicroRNAs miR143 and
miR145, targets of serum response factor, myocardin, and NK2 transcription factor-
related homeobox protein NKx2-5, are cotranscribed in murine multipotent cardiac
progenitors that give rise to vascular smooth myocytes [ 777 ]. 45 MicroRNA-145
is necessary for myocardin-induced reprogramming of fibroblasts into smooth
myocytes and sufficient to provoke differentiation of multipotent neural-crest stem
cells into vascular smooth myocytes. MicroRNAs miR143 and miR145 coopera-
tively works on a set of transcription factors, such as Kr uppel-like factor KLF4,
myocardin, and member of ETS family ELk1, to promote differentiation and repress
proliferation of smooth myocytes.
In coronary artery smooth myocytes, adenosine A 1 receptor coupled to

G-protein subunits of the G pathway

that causes phosphorylation of extracellular signal-regulated protein kinases ERK1
and ERK2 [ 778 ].
The glycoprotein elastin microfibril interfacer-1 (emilin-1) is secreted in the
extracellular matrix. Emilin-1 coexpressed with transforming growth factor-

α i / o subclass activates the PLC β 3-PKC α

in
vascular smooth myocytes is a negative regulator of transforming growth factor-

β

β

signaling. Emilin-1, once bound to proTGF β 1 in the extracellular space prevents

the production of active TGF 1[ 779 ]. Moreover, emilin-1 regulates blood vessel

caliber and peripheral resistances, hence blood pressure. In the absence of emilin-1,
the blood vessel bore is reduced; peripheral resistances and blood pressure thereby
increase.
Coupling factor-6 (CF6) is a component of mitochondrial ATP synthase. It is re-
leased from endothelial cells by tumor-necrosis factor-

β

α and hemodynamic stresses

via activation of nuclear factor- B. Adenosine triphosphate synthase bound to the

plasma membrane of vascular endothelial cells acts as a CF6 receptor. Coupling
factor-6 increases the concentration of intracellular protons by activating ATPase. In
smooth myocytes of resistance arterioles, CF6 causes vasoconstriction by inhibiting
phospholipase-A2 and lowering endothelial generation of prostacyclin. However,
direct vasoconstriction occurs in an auto- or paracrine fashion, independently of
decrease in endothelium-induced vasodilation. Coupling factor-6 also induces a
monophasic increase in intracellular calcium concentration in smooth myocytes and
enhances angiotensin-2-induced Ca 2 + spikes via activated Src kinase [ 780 ].
Protein Tyr kinase Src regulates numerous mediators of vasoconstriction and in-
tervenes in intracellular acidosis. Activated Src enhances Ca V 1.2 channels and Ca 2 +
release from intracellular stores in response to angiotensin-2, as it phosphorylates
Ca 2 + channel and phospholipase-C

κ

1.
Anticoagulant and anti-inflammatory thrombomodulin is not detected in
quiescent vascular smooth myocytes, but is expressed by these cells in diseased
vessels. In cultured vascular smooth myocytes, thrombin, cAMP, and COx2-derived

γ

45 Multipotent cardiac progenitors can differentiate into cardiomyocytes, vascular smooth my-
ocytes, and endothelial cells.