Vascular smooth muscle cells (VSMCs),
unlike other muscle cells, do not terminally differentiate.
In response to injury, VSMCs
change phenotype, proliferate and migrate as
part of the repair process. Dysregulation of this
plasticity program contributes to the pathogenesis
of several vascular disorders, such as
atherosclerosis, restenosis and hypertension.
The discovery of mutations in the gene encoding
BMPRII, the type II subunit of the receptor
for Bone Morphogenetic Proteins (BMPs), in
patients with pulmonary arterial hypertension
(PAH) provided an indication that BMP signaling
may affect the homeostasis of VSMCs and
their phenotype modulation. Here we report
that BMP signaling potently induces SMCspecific
genes in pluripotent cells, and prevents
dedifferentiation of arterial SMCs. The BMPinduced
phenotype switch requires intact
RhoA/ROCK signaling, but is not blocked by
inhibitors of the TGFß and PI-3K/Akt pathways.
Furthermore, nuclear localization and
recruitment of the myocardin-related transcription
factors (MRTF-A and MRTF-B) to a
SM a-actin (SMA) promoter is observed in response
to BMP treatment. Thus, BMP signaling
modulates VSMC phenotype via cross talk with
the RhoA/MRTFs pathway, and may contribute
to the development of the pathological
characteristics observed in patients with PAH
and other obliterative vascular diseases.

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