Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology
Biomolecules,
Год журнала:
2024,
Номер
14(2), С. 140 - 140
Опубликована: Янв. 23, 2024
A
monolayer
of
endothelial
cells
(ECs)
lines
the
lumen
blood
vessels
and,
as
such,
provides
a
semi-selective
barrier
between
and
interstitial
space.
Compromise
lung
EC
due
to
inflammatory
or
toxic
events
may
result
in
pulmonary
edema,
which
is
cardinal
feature
acute
injury
(ALI)
its
more
severe
form,
respiratory
distress
syndrome
(ARDS).
The
functions
are
controlled,
at
least
part,
via
epigenetic
mechanisms
mediated
by
histone
deacetylases
(HDACs).
Zinc-dependent
HDACs
represent
largest
group
activated
Zn2+.
Members
this
HDAC
involved
regulation
primarily
modifying
structure
chromatin
upon
removal
acetyl
groups
from
histones.
In
addition,
they
can
deacetylate
many
non-histone
proteins,
including
those
located
extranuclear
compartments.
Recently,
therapeutic
potential
inhibiting
zinc-dependent
for
preservation
has
gained
momentum.
However,
role
specific
subtypes
remains
largely
unknown.
This
review
aims
provide
an
update
on
dysfunction
related
diseases.
We
will
broadly
focus
biological
contributions,
signaling
pathways
transcriptional
roles
pathobiology
associated
mainly
with
diseases,
we
discuss
their
inhibitors
prevention.
Язык: Английский
Hydrazides as Inhibitors of Histone Deacetylases
Journal of Medicinal Chemistry,
Год журнала:
2024,
Номер
67(16), С. 13512 - 13533
Опубликована: Авг. 2, 2024
In
this
Perspective,
we
have
brought
together
available
biological
evidence
on
hydrazides
as
histone
deacetylase
inhibitors
(HDACis)
and
a
distinct
type
of
Zn-binding
group
(ZBG)
to
be
reviewed
for
the
first
time
in
literature.
N-Alkyl
transformed
field,
providing
innovative
practical
chemical
tools
selective
effective
inhibition
specific
(HDAC)
enzymes,
addition
usual
hydroxamic
acid
o-aminoanilide
ZBG-bearing
HDACis.
This
has
enabled
efficient
targeting
neurodegenerative
diseases
such
Alzheimer's
disease,
cancer,
cardiovascular
diseases,
protozoal
pathologies.
Язык: Английский
Zinc-Dependent Histone Deacetylases in Lung Endothelial Pathobiology
Опубликована: Янв. 3, 2024
A
monolayer
of
endothelial
cells
(ECs)
lines
the
lumen
blood
vessels
and
as
such
provides
a
semi-selective
barrier
between
interstitial
space.
Compromise
lung
EC
due
to
inflammatory
or
toxic
events
may
results
in
pulmonary
edema,
which
is
cardinal
feature
acute
injury
(ALI)
its
more
severe
form,
respiratory
distress
syndrome
(ARDS).
The
functions
are
controlled,
at
least
part,
via
epigenetic
mechanisms
mediated
by
histone
deacetylases
(HDACs).
Zinc-dependent
HDACs
represent
largest
group
activated
Zn2+.
Members
this
HDAC
involved
regulation
primarily
modifying
structure
chromatin
upon
removal
acetyl
groups
from
histones.
In
addition,
they
can
deacetylate
many
non-histone
proteins,
including
those
located
extra
nuclear
compartments.
Recently,
therapeutic
potential
inhibiting
zinc-dependent
for
preservation
has
gained
momentum.
However,
role
specific
subtypes
remains
largely
unknown.
This
review
aims
provide
an
update
on
dysfunction
related
diseases.
We
will
broadly
focus
biological
contributions,
signaling
pathways
transcriptional
roles
pathobiology
associated
mainly
with
diseases
we
discuss
their
inhibitors
prevention.
Язык: Английский
Vascular Endothelial Growth Factor and the Pathogenesis of Intracranial Aneurysms: A Systematic Review on the Missing Link in a Complex Pathway
Journal of the American Heart Association,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 22, 2024
Background
Aneurysms
are
one
of
the
most
common
and
yet
devastating
cerebrovascular
diseases
after
rupture.
Despite
several
decades
scientific
advancements
including
expansion
endovascular
capabilities
noninvasive
imaging
modalities,
no
medical
treatment
exists
to
date.
This
failure
is
likely
largely
attributed
complex
multifactorial
nature
aneurysm
pathophysiology.
Recent
research
has
increasingly
implicated
vascular
endothelial
growth
factor
(VEGF)
in
development
rupture
intracranial
aneurysms.
Regarded
as
potent
inducers
angiogenesis,
it
a
key
wall
maintenance,
inflammation,
regulation
permeability.
Whether
abnormal
VEGF
expression
directly
related
or
acting
merely
an
acute
phase
reactant
remains
uncertain.
No
review
current‐state‐of‐evidence
on
this
topic
yet.
Methods
Results
A
systematic
literature
search
was
performed
following
PRISMA
guidelines
May
2024
that
queried
PubMed
(1946–2024),
Wiley
Cochrane
Library:
Central
Register
Controlled
Trials
(1898–2024),
Thompson
Reuters
Web
Science:
Citation
Index
(1900–2024),
Google
Scholar
(1946–2024).
Inclusion
criteria
encompassed
human
animal
studies
investigated
relationship
VEGF.
Several
models
revealed
significantly
elevated
tissue,
along
with
greater
levels
cerebrospinal
fluid
systemically.
Overexpression
been
shown
inhibit
cell
migration,
proliferation,
induce
apoptosis.
Recently,
genetic
polymorphisms
have
also
correlate
presence
aneurysms,
establishing
first
link
between
two.
Conclusions
lacking
definitive
evidence
causal
relationship,
wealth
supporting
data
substantiates
promising
for
future
investigation
into
pathophysiology
potential
therapeutic
target.
Язык: Английский
Circulating Inflammatory Cytokines and Risk of Intracranial Aneurysm: A Mendelian-randomization Study
medRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 18, 2023
Abstract
Background
Multiple
studies
have
established
the
significant
influence
of
inflammatory
factors
on
initiation
and
advancement
intracranial
aneurysm
(IA).
However,
causality
between
specific
cytokines
IA
remains
uncertain.
This
study
aims
to
elucidate
it
using
Mendelian
randomization
(MR).
Methods
The
genetic
data
were
collected
from
a
genome-wide
association
(GWAS)
conducted
circulating
in
Finnish
population,
involving
characteristics
41
obtained
through
meta-analysis
8,293
samples.
for
derived
most
extensive
GWAS
study,
which
included
7,495
samples
individuals
European
ancestry
71,934
healthy
control
subjects.
inverse
variance
weighted
method
primarily
determined
causal
correlation
exposures
outcomes.
In
addition,
other
robust
MR
analysis
methods
sensitivity
analyses
utilized
guarantee
accuracy
results.
Results
Our
results
indicate
negative
IP-10
unruptured
aneurysms
(UIA)
(odds
ratio,
OR:
0.63,
95%CI:
0.45-0.9,
p=0.01).
IL-10
VEGF
exhibit
positive
with
aneurysmal
subarachnoid
hemorrhage
(aSAH)
(OR:
1.19,
1.02-1.39,
p=0.024;
1.12,
1.01-1.23,
p=0.025).
levels
FGFBasic
TRAIL
aSAH.
0.62,
0.42-0.92,
p=0.018;
0.89,
0.8-1,
p=0.041).
increased
IL-12p70,
IL-4,
IFNg,
IL-10,
IL-17,
IL-1ra,
IL-6,
IL-9,
VEGF,
observed
as
consequence
IA.
(Beta:
0.18,
0.08-0.28,
p=6.2e-4;
Beta:
0.15,
0.07-0.23,
p=2e-4;
p=3.5e-4;
0.13,
0.05-0.21,
p=1.4e-3;
0.1,
0.02-0.18,
p=0.015;
0.17,
0.02-0.32,
p=0.031;
0.14,
0.05-0.32,
p=0.003;
0.01-0.24,
p=0.035;
0.05-0.23,
p=0.002;
0.09,
0.01-0.17,
p=0.032).
Conclusion
suggests
that
may
serve
protective
factor
UIA.
demonstrated
defensive
impact
against
aSAH,
while
been
identified
elevate
risk
rupture.
Additionally,
various
are
due
pathogenesis,
these
function
controlling
inflammation
progression
Язык: Английский