Smooth Myocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 422

prostaglandins, such as PGe2 and PGi2, upregulate thrombomodulin expression.
Platelet-derived growth factor-BB, a potent mitogen and chemoattractant of smooth
myocytes, induces thrombomodulin expression via the Src-PI3K-PKB-TOR
signaling pathway and transcription factor E26-transformation-specific sequence
ETS1 that activates the thrombomodulin gene promoter [ 781 ].
Prorenin receptor (PRR) is expressed in smooth muscle cells of human mammary
arteries among others. Prorenin, an inactive proenzyme, can thus function indepen-
dently of angiotensin-1 production from angiotensinogen (secreted out of the liver)
by renin aspartyl protease (angiotensinogenase). Prorenin binds PRR 3-times more
efficiently than renin. Prorenin causes SMC migration. It indeed increases via PRR
the intracellular levels of RhoA GTP and Rac1 GTP [ 782 ]. In addition, tethering of
prorenin to PRR triggers activation of extracellular signal-regulated kinases ERK1
and ERK2 and phosphorylation of heat shock protein HSP27, 46 thereby promoting
cell proliferation and contractility. Prorenin also triggers the formation of larger
focal adhesions as well as cleavage of focal adhesion kinase FAK1, a regulator of
cell migration, into 2 fragments by calpain. Processing of FAK1 enzyme is a marker
of focal adhesion disassembly required for cell rear retraction during motion.
Arterial smooth myocytes express surfactant protein SPd involved in innate
immunity, especially in defense against lung pathogens, hence directly protecting
the vessel wall [ 783 ]. Surfactant protein-D attenuates the release of interleukin-8
stimulated by lipopolysaccharide and tumor-necrosis factor- , thereby repressing

inflammation. Interleukin-8 indeed supports the recruitment of monocytes and neu-
trophils. Conversely, both lipopolysaccharide and TNF

α

α promote SPd expression.

8.5.7 Vascular Smooth Myocyte Migration

Migration of vascular smooth myocyte occurs during angiogenesis and wound
healing, as well as atherogenesis and after stent implantation. 47 Numerous pro- and
antimigratory molecules influence SMC movement (Table 8.15 ). Migratory stimuli
activate signaling cascades that trigger remodeling of cytoskeleton (actin filaments,
microtubules, and intermediate filaments) and focal adhesions as well as activation
of cellular nanomotors such as those associated with actomyosin filaments (Vol. 2 -
Chap. 6. Cell Motility). 48

46 Protein HSP27 is involved in SMC contractility, cytoskeleton reorganization, and cell migration.
47 During atherogenesis, vascular smooth myocytes migrate to intima from the media. In addition,
CD34 hematopoietic progenitor cells can migrate from blood circulation to give rise to smooth

myocyte progenitors.
48 During cell movements, the nucleus moves toward the cell rear. The PI3K

+

γ β

-PKB-GSK3 axis

acts via adenomatous polyposis coli protein that interacts with microtubules [ 784 ].