Dysfunction of Endothelial Cell Precursors in Heart Failure Development Volume 1 - Issue 3
Alexander E Berezin*
Department of internal medical, State Medical University of Zaporozhye, Ukraine
Received: August 12, 2017; Published: August 29, 2017
Corresponding author : Alexander E Berezin, Senior Consultant of Therapeutic Unit, Internal Medicine Department, State Medical University of
Zaporozhye, Ukraine
Heart failure (HF) a leading cause of premature death in patients with established cardiovascular (CV) disease. Although the global burden
of HF is increasing, there is no evidence regarding promising results that improves long-term clinical outcomes especially for HF with preserved
and mid-regional pump function. In this context, determination of the vulnerable populations at higher risk of HF development and progression
is very promising. Endothelial dysfunction (ED) plays a central role in the manifestation of HF regardless its phenotypes. There is a large body
of evidence regarding that the endothelial progenitor cells (EPCs) as a component of endogenous vascular repair system could be modified by
several stimuli including epigenetic factors and thereby they are involved in the pathogenesis of ED. However, there is unclear whether EPC
dysfunction is only whiteness of HF or it could be a factor of HF manifestation in vulnerable population. The short communication is depicted
the uncertain role of EPC dysfunction in pathogenesis of HF.
Heart failure (HF) remainsa leading cause of mortality in
patients with established cardiovascular (CV) disease [1,2].
Currently there is a strong trend toward reducing death rate
due to HF associated with steady increased frequencies of newly
manifested HF in developed countries, although in developing
countries the HF mortality rate appears to be exaggeratedly high
[3]. Identification of the vulnerable populations at higher risk of HF
development and progression is now based on the early diagnosis
of CV disease (atherosclerosis, hypertension, coronary heart
disease, peripheral artery disease, and vasculitis) and metabolic
states including diabetes, abdominal obesity, thyroid dysfunction,
as well as other CV risk factors which may pre-exist CV diseases and
particularly HF [4].
Endothelial dysfunction (ED) is considered an integral state
in the development of HF regardless its phenotypes [5] and even
contributes in clinical outcomes across all stages of CV continuum
[6]. There is a large body of evidence regarding that the exhausted
reparative ability of vasculature in resulting in several factors
including pre-existing co-morbidities, some severe diseases
that had appeared prior HF manifestation (trauma, infections,
inflammatory diseases), and CV risk factors could be primary
reasons for loss of endothelial cell integrity and shaping ED [7-9].
In this context, endothelial progenitor cells (EPCs) that are mobbed
from bone marrow precursors and peripheral tissue residences
and involved in reparative processes through differentiation and
turn-into mature endothelial cells are promising biomarkers of ED
with possible predictive value [10,11]. Indeed, decreased number
of circulating EPCs was found a strong predictor of CV death, CV
outcomes and HF-related events in HF patients with reduced and
preserved left ventricular ejection fraction independently etiology
of the disease [12-14].
On the other hand, EPCs that circulate in the peripheral blood
in patients at higher risk of HF and in individuals with established
HF presented lowered survival ability and partially inconvenience
to be differentiated to mature endothelial cells under influence
of essential innate stimuli including transforming growth factorbeta,
tumor necrosis factor-alpha (TNF-α) and other inflammatory
cytokines [15,16]. This phenomenon was previously described as
EPC dysfunction and it was widely diagnosed in the patients with
diabetes, abdominal obesity, hypertension and other CV risk factors
[17]. Interesting, that all these factors promote oxidative stress and
mitochondrial dysfunction in target cells including EPCs that is
suitable for different path physiological stages of HF.
Although number and functionality of EPCs have validated to be
strong predictors of HF risk development and advance, it had been
remained unclear whether EPC dysfunction is only whiteness of HF
or it could be a factor of HF manifestation in vulnerable population.
However, recent clinical trials have not confirmed ability of EPC collected from the patients with established HF having recovered
function after treatment including cardiac rehabilitation programs,
while a number of circulating EPCs may recover completely
in some cases [18-20]. It has been suggested that the altered
immune pattern of EPCs, which could be determined prior HF,
is central player in worsening vascular / endothelial reparation
and contributes in ED [21]. Probably EPC functionality could be
regulated by some epigenetic factors influencing on ability of
precursors to differentiate into mature cells including endothelial
cells. Moreover, it has noted that there is possibility to change of
endothelial cell immune phenotype to cardiac cell phenotype
in animal model [22]. Whether similar effects trigger structure
and functional abnormality in cell precursors that involve in the
pathogenesis of HF is not well established, although accumulation
of reactive oxygen species leading to the swelling and fragmentation
of mitochondria of EPCs has now described as factor of decreased
repair ability of precursors [23]. Indeed, enhancement of oxidative
stress and mitochondrial dysfunction of EPCs may negatively
effect of number and function of one’s (mobbing, proliferation,
regeneration, apoptosis, differentiation, cell-cell interaction,
survival) through intracellular signaling pathways (Akt/nitric oxide,
PI3K/nitric oxide), which may operate in signal-regulated kinase
and the inflammatory genes expression, such as interleukin-6 and
TNF-α, and synthesis of specific miRNAs (-126, -128, -130) [24,25].
Finally, epigenetically modified EPCs are not able to maintain the
homeostasis of vasculature and trigger inadequate endothelial
responses that realize ED and microvascular inflammation.
Probably, this model may be taken into consideration for creating
novel molecular biomarkers of HF and target for personal treatment
of the disease.
Evidence emerging from both animal and clinical studies has
shown that EPC dysfunction may be crucial for pathogenesis of HF
and however it is not excluded that worsening endogenous vascular
repair system including EPCs could play a pivotal role in the
manifestation and progress of HF regardless etiology of the disease.
Biomarker strategy based on determination of EPC dysfunction in
patients at higher risk of HF and in individuals with established HF
maybe promising for HF diagnosis and stratification in future, while
this conception requires more investigations for understanding.
ISSN: 2574 -1241
