Cardiovascular Research,
Год журнала:
2023,
Номер
119(13), С. 2262 - 2277
Опубликована: Авг. 18, 2023
Abstract
Pulmonary
arterial
hypertension
(PAH)
is
a
rare
cardiovascular
disorder
leading
to
pulmonary
and,
often
fatal,
right
heart
failure.
Sex
differences
in
PAH
are
evident,
which
primarily
presents
with
female
predominance
and
increased
male
severity.
Disturbed
signalling
of
the
transforming
growth
factor-β
(TGFβ)
family
gene
mutations
bone
morphogenetic
protein
receptor
2
(BMPR2)
risk
factors
for
development,
but
how
sex-specific
cues
affect
TGFβ
remains
poorly
understood.
In
this
review,
we
aim
explore
sex
bias
by
examining
through
mechanistical
translational
evidence.
hormones
including
oestrogens,
progestogens,
androgens,
can
determine
expression
receptors
(including
BMPR2),
ligands,
soluble
antagonists
within
tissue-specific
manner.
Furthermore,
sex-related
genetic
processes,
i.e.
Y-chromosome
X-chromosome
inactivation,
influence
at
multiple
levels.
Given
clinical
similarities,
expect
that
conclusions
arising
from
review
may
apply
also
hereditary
haemorrhagic
telangiectasia
(HHT),
vascular
affecting
pathway.
summary,
anticipate
investigating
manner
will
contribute
further
understand
underlying
processes
likely
HHT.
Journal of Personalized Medicine,
Год журнала:
2023,
Номер
13(2), С. 366 - 366
Опубликована: Фев. 19, 2023
Pulmonary
vascular
remodeling
is
the
critical
structural
alteration
and
pathological
feature
in
pulmonary
hypertension
(PH)
involves
changes
intima,
media
adventitia.
consists
of
proliferation
phenotypic
transformation
artery
endothelial
cells
(PAECs)
smooth
muscle
(PASMCs)
middle
membranous
artery,
as
well
complex
interactions
involving
external
layer
fibroblasts
(PAFs)
extracellular
matrix
(ECM).
Inflammatory
mechanisms,
apoptosis
other
factors
wall
are
influenced
by
different
mechanisms
that
likely
act
concert
to
drive
disease
progression.
This
article
reviews
these
highlights
some
pathogenetic
involved
process.
Communications Biology,
Год журнала:
2025,
Номер
8(1)
Опубликована: Янв. 8, 2025
Abstract
Blood
vessel
formation
relies
on
biochemical
and
mechanical
signals,
particularly
during
sprouting
angiogenesis
when
endothelial
tip
cells
(TCs)
guide
through
filopodia
formation.
The
contribution
of
BMP
receptors
in
defining
tip-cell
characteristics
is
poorly
understood.
Our
study
combines
genetic,
biochemical,
molecular
methods
together
with
3D
traction
force
microscopy,
which
reveals
an
essential
role
BMPR2
for
actin-driven
properties
(ECs).
Targeting
Bmpr2
reduced
zebrafish
BMPR2-deficient
human
ECs
formed
fewer
filopodia,
affecting
cell
migration
actomyosin
localization.
Spheroid
assays
revealed
a
fibrin
gels.
Even
more
strikingly,
mosaic
spheroids,
failed
to
acquire
positions.
Yet,
microscopy
that
these
distinct
behaviors
cannot
be
explained
by
differences
force-induced
matrix
deformations,
even
though
adopted
cone-shaped
morphologies.
Notably,
positively
regulates
local
CDC42
activity
at
the
plasma
membrane
promote
findings
reveal
functions
as
nexus
integrating
biomechanical
processes
crucial
TCs
angiogenesis.
American Journal of Respiratory and Critical Care Medicine,
Год журнала:
2020,
Номер
203(11), С. 1419 - 1430
Опубликована: Дек. 15, 2020
Pulmonary
endothelial
permeability
contributes
to
the
high-permeability
pulmonary
edema
that
characterizes
acute
respiratory
distress
syndrome.
Circulating
BMP9
(bone
morphogenetic
protein
9)
is
emerging
as
an
important
regulator
of
vascular
homeostasis.
Frontiers in Cardiovascular Medicine,
Год журнала:
2021,
Номер
8
Опубликована: Сен. 17, 2021
Atherosclerosis
is
a
fundamental
disease
of
the
cardiovascular
system
that
leads
to
high
morbidity
and
mortality
worldwide.
The
endothelium
first
protective
barrier
in
atherosclerosis.
Endothelial
cells
have
potential
be
transformed
into
mesenchymal
cells,
process
termed
endothelial
transition
(EndMT).
On
one
hand,
EndMT
known
contribute
atherosclerosis
by
inducing
number
phenotypes
ranging
from
cell
dysfunction
plaque
formation.
other
risk
factors
for
can
lead
EndMT.
A
substantial
body
evidence
has
suggested
induces
development
atherosclerosis;
therefore,
deeper
understanding
molecular
mechanisms
underlying
might
provide
insights
reverse
this
condition.
Pulmonary
arterial
hypertension
(PAH)
is
a
rare
disease
characterized
by
high
blood
pressure
in
the
pulmonary
circulation
driven
pathological
remodeling
of
distal
arteries,
leading
typically
to
death
right
ventricular
failure.
Available
treatments
improve
physical
activity
and
slow
progression,
but
they
act
primarily
as
vasodilators
have
limited
effects
on
biological
cause
disease—the
uncontrolled
proliferation
vascular
endothelial
smooth
muscle
cells.
Imbalanced
signaling
transforming
growth
factor-β
(TGF-β)
superfamily
contributes
extensively
dysregulated
cell
PAH,
with
overactive
pro-proliferative
SMAD2/3
occurring
alongside
deficient
anti-proliferative
SMAD1/5/8
signaling.
We
review
TGF-β
mechanisms
underlying
PAH
pathogenesis,
interactions
inflammation
mechanobiological
forces,
therapeutic
strategies
under
development
that
aim
restore
SMAD
balance
diseased
vessels.
These
could
potentially
reverse
targeting
causative
therefore
hold
significant
promise
for
patient
population.
Circulation,
Год журнала:
2024,
Номер
150(16), С. 1268 - 1287
Опубликована: Авг. 22, 2024
BACKGROUND:
Integrative
multiomics
can
elucidate
pulmonary
arterial
hypertension
(PAH)
pathobiology,
but
procuring
human
PAH
lung
samples
is
rare.
METHODS:
We
leveraged
transcriptomic
profiling
and
deep
phenotyping
of
the
largest
multicenter
biobank
to
date
(96
disease
52
control)
by
integration
with
clinicopathologic
data,
genome-wide
association
studies,
Bayesian
regulatory
networks,
single-cell
transcriptomics,
pharmacotranscriptomics.
RESULTS:
identified
2
potentially
protective
gene
network
modules
associated
vascular
cells,
we
validated
ASPN
,
coding
for
asporin,
as
a
key
hub
that
upregulated
compensatory
response
counteract
PAH.
found
asporin
in
lungs
plasma
multiple
independent
cohorts
correlates
reduced
severity.
show
inhibits
proliferation
transforming
growth
factor–β/phosphorylated
SMAD2/3
signaling
artery
smooth
muscle
cells
from
lungs.
demonstrate
Sugen-hypoxia
rats
knockdown
exacerbated
recombinant
attenuated
CONCLUSIONS:
Our
integrative
systems
biology
approach
dissect
transcriptome
uncovered
novel
target
therapeutic
potential
