3.11 PAH and EPCs
The usual hypothesis is that a low level of EPCs is one of the
conditions for the occurrence of PAH. In research regarding congenital
heart disease (CHD) that caused PAH in childhood, severe PAH patients
(mean pulmonary arterial pressure > 25 mmHg) show a
significantly lower EPC level as compared to non-PAH patients. This
phenomenon shows that low level of EPCs is strongly correlated with PAH.
However, this relationship was not apparent for patients with mild PAH,
indicating that a decreased level of EPC is not the only pathogenesis,
or the EPC level will not be significantly decreased in the early stage
of PAH(H. X. Sun et al., 2019). The same result was also obtained for
adult patients, and in a comparison of COPD and COPD-PAH patients, the
latter group showed a significantly lower EPC level as compared to COPD
patients(P. Liu et al., 2016). A different conclusion was reached by a
group of English scientists, who found that the level of EPCs was
increased in idiopathic pulmonary arterial hypertension (iPAH) patients
with bone morphogenetic protein type II receptor (BMPR2) mutation (which
is a classical mutation that results in the development of iPAH).
In order to explain this aberration, a comparison was made between the
EPC screening conditions in different studies (Table 1). We found that
almost all scientists use different testing conditions, and the
different markers may correspond to different cell groups and different
cell functions, finally leading to the chaos of conclusions(Toshner et
al., 2009). These different definitions of EPCs cause academic
disruption that increases the difficulty and cost of discussions and
experiments, and eventually leads to the standstill of progress. Despite
the existence of contrary opinions, there is a consensus by most
scientists that the low level of EPCs is part of an indispensable
process that results in the development of PAH. They suggest that in the
initial stage of PAH, high levels of cycling EPCs are able to repair the
loss of vessels. However, with the progression of disease, the
continuous damage exceeds the compensatory ability of EPCs, which
finally leads to the reduction of peripheral EPCs and additional
destruction of vessel structure. Ultimately, this process causes stiffer
and narrower vessels and a higher pulmonary arterial pressure.
Under this vicious cycle, the symptoms of PAH become increasingly severe
and finally lead to death(Toshner et al., 2009). EPCs exist in numerous
ways to prevent the development and reverse existing PAH, and mainly
include direct incorporation to sites of impaired vessels for repair,
playing supportive roles in cellular repair, inhibiting the transfer of
ECs, and participating in immunosuppression functions and secretion
functions such as secretome, exosome and extracellular vehicles
(EVs)(Bayraktutan, 2019; Bianconi et al., 2018; Wei et al., 2013).