Acta Biochimica et Biophysica Sinica,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 1, 2024
Fibrosis
is
the
main
pathological
feature
of
aortic
stiffness,
which
a
common
extracardiac
comorbidity
heart
failure
with
preserved
ejection
fraction
(HFpEF)
and
contributor
to
left
ventricular
(LV)
diastolic
dysfunction.
Systemic
low-grade
inflammation
plays
crucial
role
in
pathogenesis
HFpEF
development
vascular
fibrosis.
In
this
study,
we
investigate
inflammatory
mechanism
fibrosis
using
novel
mouse
model.
LV
dysfunction
induced
by
high-fat
diet
(HFD)
combined
subcutaneous
aldosterone
infusion
are
utilized.
The
constructed
model
exhibits
augmented
macrophage
recruitment
NLR
family
pyrin
domain
containing
3
(NLRP3)-dependent
interleukin
(IL)-1β
production
fibrotic
aortas.
addition,
bone
marrow
transplant
employed
induce
macrophage-specific
NLRP3
deficiency
These
mice
show
almost
completely
suppressed
cleaved-caspase-1
mature
IL-1β
protein
expression
aortas,
indicating
that
inflammasome
activation
enhances
overproduction
Furthermore,
inhibition
improves
conclusion,
study
demonstrates
pivotal
effect
NLRP3-dependent
on
cardiac
function
HFpEF,
suggesting
potential
target
for
therapy.
Advanced Science,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 16, 2024
Abstract
The
global
incidence
of
metabolic
dysfunction‐associated
fatty
liver
disease
(MAFLD)
has
risen
sharply.
This
condition
is
strongly
associated
with
the
risk
cardiovascular
(CVD),
but
how
MAFLD
affects
development
and
progression
CVD,
particularly
concerning
vascular
calcification,
remains
unclear.
Herein,
extracellular
vesicles
(EVs)
are
identified
from
steatotic
hepatocytes
as
a
trigger
that
accelerated
both
intimal
medial
calcification.
Steatotic
found
to
release
more
EVs,
which
able
reach
tissue,
be
taken
up
by
smooth
muscle
cells
(VSMCs),
promote
their
osteogenic
differentiation.
Within
these
toxic
vesicles,
protein
cargo
called
lectin
galactoside‐binding
soluble
3
binding
(Lgals3bp)
acted
potent
inducer
osteochondrogenic
transformation
in
VSMCs.
Both
inhibition
EV
liver‐specific
knockdown
Lgals3bp
profoundly
attenuated
work
partially
explains
reason
for
high
calcification
unveils
novel
mechanism
may
used
prevent
or
treat
complications
patients
MAFLD.
Acta Biochimica et Biophysica Sinica,
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 1, 2024
Fibrosis
is
the
main
pathological
feature
of
aortic
stiffness,
which
a
common
extracardiac
comorbidity
heart
failure
with
preserved
ejection
fraction
(HFpEF)
and
contributor
to
left
ventricular
(LV)
diastolic
dysfunction.
Systemic
low-grade
inflammation
plays
crucial
role
in
pathogenesis
HFpEF
development
vascular
fibrosis.
In
this
study,
we
investigate
inflammatory
mechanism
fibrosis
using
novel
mouse
model.
LV
dysfunction
induced
by
high-fat
diet
(HFD)
combined
subcutaneous
aldosterone
infusion
are
utilized.
The
constructed
model
exhibits
augmented
macrophage
recruitment
NLR
family
pyrin
domain
containing
3
(NLRP3)-dependent
interleukin
(IL)-1β
production
fibrotic
aortas.
addition,
bone
marrow
transplant
employed
induce
macrophage-specific
NLRP3
deficiency
These
mice
show
almost
completely
suppressed
cleaved-caspase-1
mature
IL-1β
protein
expression
aortas,
indicating
that
inflammasome
activation
enhances
overproduction
Furthermore,
inhibition
improves
conclusion,
study
demonstrates
pivotal
effect
NLRP3-dependent
on
cardiac
function
HFpEF,
suggesting
potential
target
for
therapy.
