Cardiovascular dysfunction and altered lysosomal signaling in a murine model of acid sphingomyelinase deficiency
Journal of Molecular Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 15, 2025
Язык: Английский
ACLY Promotes Cardiac Fibrosis via the Regulation of DNL and Histone Acetylation
Hypertension,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 6, 2025
ATP
citrate
lyase
(ACLY)
is
a
key
enzyme
in
de
novo
lipogenesis
that
generates
acetyl-CoA
from
citrate.
Although
fatty
acids
are
required
for
energy
production
and
biomass
synthesis
the
heart,
regulatory
mechanisms
of
ACLY-mediated
pathological
cardiac
fibroblasts
remain
unknown.
The
aim
this
study
was
to
investigate
biological
role
ACLY
remodeling.
Adeno-associated
virus
serotype
9-mediated
shRNA
targeting
Acly
intravenously
injected
into
C57BL/6J
male
mice.
mice
were
subsequently
continuously
infused
with
mixture
angiotensin
II
phenylephrine.
Cardiac
phenotypes
evaluated
via
histological
staining.
Cell
proliferation
assays,
stable
isotope
tracing
13C-labeled
glucose,
chromatin
immunoprecipitation
assays
performed
using
human
fibroblasts.
expression
upregulated
heart
sections
treated
II/phenylephrine,
particular
fibrotic
areas.
Masson
trichrome
staining
revealed
gene
silencing
significantly
reduced
fibrosis
these
Both
siRNA-mediated
knockdown
pharmacological
inhibition
suppressed
fibrous
proteins
cultured
stimulated
transforming
growth
factor-β.
Mechanistically,
lipogenesis,
limiting
acid
supply
essential
cellular
proliferation.
It
also
decreased
H3K9
H3K27
acetylation,
addition
presence
acetylated
at
promoter
regions
genes.
Our
findings
demonstrate
plays
an
important
maladaptive
fibrosis.
could
be
novel
therapeutic
target
prevent
development
failure.
Язык: Английский
MMP3 as a new target of Danshensu/tetramethylpyrazine derivative for attenuating cardiac fibrosis post-myocardial infarction
Life Sciences,
Год журнала:
2025,
Номер
unknown, С. 123570 - 123570
Опубликована: Март 1, 2025
Язык: Английский
Cardiovascular Dysfunction and Altered Lysosomal Signaling in a Murine Model of Acid Sphingomyelinase Deficiency
Research Square (Research Square),
Год журнала:
2025,
Номер
unknown
Опубликована: Март 20, 2025
Abstract
Niemann-Pick
Disease
(NPD)
is
a
rare
autosomal
recessive
lysosomal
storage
disorder
(LSD)
caused
by
the
deficiency
of
acid
sphingomyelinase
(ASMD),
which
encoded
Smpd1
gene.
ASMD
impacts
multiple
organ
systems
in
body,
including
cardiovascular
system.
This
study
first
to
characterize
cardiac
pathological
changes
mice
under
baseline
conditions,
offering
novel
insights
into
implications
NPD.
Using
histological
analysis,
biochemical
assays,
and
echocardiography,
we
assessed
function
Smpd1−/−
compared
Smpd1+/+
littermate
controls.
Immunofluorescence
assays
demonstrated
that
induced
dysfunction,
as
evidenced
accumulation
lysosomal-associated
membrane
proteins,
protease,
autophagosomes
pericytes
cardiomyocytes.
dysfunction
was
accompanied
cardiomyocytes
inflammation,
characterized
increased
expression
caspase1
inflammatory
cytokines,
infiltration
cells
tissues
mice.
In
addition,
analysis
revealed
lipid
deposition
steatosis,
along
with
pericyte-to-myofibroblast
transition
(PMT)
interstitial
fibrosis
Moreover,
echocardiography
further
developed
coronary
microvascular
(CMD),
decreased
blood
flow
velocity
arteriolar
wall
thickness.
Additionally,
these
exhibited
significant
impairments
systolic
diastolic
function,
shown
reduced
ejection
fraction
prolonged
left
ventricular
relaxation
time
constant
(Tau
value).
These
findings
suggest
induces
profound
vascular
myocardium,
potentially
driven
mechanisms
involving
well
both
inflammation.
Язык: Английский
Causes, Diagnosis, Treatment, and Prognosis of Cardiac Fibrosis: A Systematic Review
Hasan A BaniHani,
Lana H Khaled,
Nada M Al Sharaa
и другие.
Cureus,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 27, 2025
Cardiac
fibrosis,
characterized
by
excessive
extracellular
matrix
deposition,
contributes
to
heart
failure,
arrhythmias,
and
myocardial
dysfunction.
Despite
advances
in
understanding
its
mechanisms,
targeted
antifibrotic
therapies
remain
limited.
This
review
examines
the
causes,
molecular
diagnostic
approaches,
therapeutic
strategies
for
cardiac
fibrosis.
A
systematic
of
peer-reviewed
studies
was
conducted,
focusing
on
etiology,
diagnosis,
treatment,
prognosis
fibrosis
with
no
specific
timeframe.
The
condition
is
driven
fibroblast
activation,
inflammatory
pathways,
mechanical
stress,
key
contributing
factors
including
ischemic
disease,
hypertension,
diabetes,
aging.
Diagnostic
tools
such
as
magnetic
resonance
imaging
T1
mapping
biomarkers
play
a
crucial
role,
natriuretic
peptides
offering
both
prognostic
value.
Galectin-3
has
also
shown
promise
marker.
Current
therapies,
RAAS
inhibitors
beta-blockers,
help
prevent
progression
but
do
not
reverse
established
Emerging
plant-based
compounds,
gene
therapy,
fibroblast-targeting
vaccines,
stem
cell
reprogramming
show
potential
preclinical
studies.
However,
remains
major
driver
disease
progression,
existing
treatments
Major
gaps
include
lack
validated
agents
challenges
translating
findings
into
clinical
applications.
Further
research
essential
develop
effective
interventions.
Язык: Английский
NOX4-driven Mitochondrial Oxidative Stress in Aging Promotes Myocardial Remodeling and Increases Susceptibility to Ventricular Tachyarrhythmia
Roberto Ramos Mondragón,
Shuyun Wang,
Mark Stevenson
и другие.
Free Radical Biology and Medicine,
Год журнала:
2025,
Номер
unknown
Опубликована: Май 1, 2025
Язык: Английский
The Macrophage–Fibroblast Dipole in the Context of Cardiac Repair and Fibrosis
Biomolecules,
Год журнала:
2024,
Номер
14(11), С. 1403 - 1403
Опубликована: Ноя. 4, 2024
Stromal
and
immune
cells
their
interactions
have
gained
the
attention
of
cardiology
researchers
clinicians
in
recent
years
as
contribution
cardiac
repair
is
increasingly
recognized.
The
process
heart
a
particularly
critical
constellation
complex
molecular
cellular
events
that
characteristically
fail
to
ensure
adequate
recovery
following
injury,
insult,
or
exposure
stress
conditions
this
regeneration-hostile
organ.
tremendous
consequence
pronounced
inability
maintain
homeostatic
states
being
translated
numerous
ways
promoting
progress
into
failure,
deadly,
irreversible
condition
requiring
organ
transplantation.
Fibrosis
fact
response
eventually
dysfunction
fibroblasts
are
major
players
process,
overproducing
collagens
other
extracellular
matrix
components
when
activated.
On
hand,
macrophages
may
differentially
affect
depending
on
status
subsets.
opposite
interaction
also
probable.
We
discuss
here
multifaceted
aspects
crosstalk
cell
dipole
opportunities
it
offer
for
beneficial
manipulation
approaches
will
hopefully
lead
disease
interventions.
Язык: Английский
Bestrahlung des Herzens zur Verbesserung der linksventrikulären Funktion
Strahlentherapie und Onkologie,
Год журнала:
2024,
Номер
200(9), С. 847 - 849
Опубликована: Июль 17, 2024
Hintergrund
Herzinsuffizienz
als
gemeinsame
Endstrecke
einer
Vielzahl
kardialer
bzw.kardiovaskulärer
Erkrankungen
ist
mit
vielen
Millionen
Betroffenen
weltweit
eine
Volkskrankheit
hohen
Mortalität
und
gravierenden
sozioökonomischen
Folgen