PKCε regulates vessel formation by peri-vascular adipose tissue (PVAT) cells

Vessel formation is crucial in tumour growth and tissue regeneration. Protein
kinase C (PKC) ε has a well-known role on hematopoietic and mesenchymal progenitor
cell differentiation and proliferation (Gobbi et al. 2013). Although PKCε has a
demonstrated role in vascular restenosis, data on PKCε and vascular progenitor differentiation
are still lacking. The aim of this work was to study the role of PKCε in
vessel formation by adult adipose tissue cell progenitors. We, first, isolated the vessel
progenitors from the adipose tissue localized between aortic arch and pulmonary
artery of adult mice by collagenase/elastase digestion followed by magnetic immunoselection
of Sca1+ cells (Passmann et al. 2008). We, then, tested their capability to
form vessels in collagen gels and to differentiate to endothelial and smooth muscle
lineage after treatment with PKCε specific activator and inhibitor peptides. The
functional experiments showed that the pharmacological activation of endogenous
PKCε abrogated tubule formation with a concomitant decrease of smooth alpha-actin
(SMA) and platelet endothelial cell adhesion molecule (PECAM) together with the
up-regulation of p-PAK1 expression. In vivo transient over-expression of PKCε significantly
reduced SMA and PECAM expression levels in vessel wall cells. Together our
data suggests that PKCε may affect vessel wall remodelling balancing the “phenotypic
switching” (Salmon et al. 2013) between the proliferative and the differentiated
state of smooth muscle and endothelial progenitor mesenchymal cells.