Pyruvate dehydrogenase alleviates macrophage autophagy in Hcy-induced ApoE<sup>-/-</sup> mice
Qiujun Liu,
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Li Feng,
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Shutong Hu
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et al.
Acta Biochimica et Biophysica Sinica,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 1, 2025
Macrophages
play
a
protective
role
in
atherosclerosis,
whereas
homocysteine
(Hcy)
is
recognized
as
an
independent
risk
factor
for
atherosclerosis.
Defects
macrophage
autophagy
contribute
to
the
formation
of
atherosclerotic
plaques,
and
dysregulated
energy
metabolism
closely
linked
process
autophagy.
However,
regulation
by
pyruvate
dehydrogenase
(PDH),
key
component
PDH
complex
involved
metabolic
homeostasis,
remains
poorly
understood
context
atherosclerosis
induced
Hcy.
In
our
study,
proteomic
profiling
identifies
748
upregulated
proteins
760
downregulated
Hcy-treated
macrophages.
KEGG
pathway
analysis
reveals
significant
enrichment
differentially
expressed
metabolism-related
pathways,
including
those
related
biosynthesis
amino
acids,
carbon
metabolism,
glycolysis/gluconeogenesis.
Additionally,
we
explore
mediating
Hcy-induced
ApoE
-/-
mice.
The
results
show
marked
reduction
expression
activity
macrophages,
leading
impaired
Notably,
activation
enhances
assembly
initiator
ULK1-FIP200-Atg13
through
modulation
AMPK/mTOR
signaling
pathway,
suggesting
potential
therapeutic
target
Language: Английский
The mitochondrial dysfunction, alongside the modifiable burden of traditional risk factors, drives the development of early-onset coronary artery disease
Frontiers in Cardiovascular Medicine,
Journal Year:
2025,
Volume and Issue:
12
Published: Feb. 19, 2025
Mitochondrial
dysfunction
is
associated
with
increased
risk
of
atherosclerosis
by
disrupting
key
cellular
processes
that
contribute
to
premature
vascular
ageing.
However,
the
specific
role
mitochondrial
in
early-onset
coronary
artery
disease
(EOCAD),
which
increasing
at
a
particularly
alarming
rate,
remains
largely
unexplored.
This
study
investigated
association
leukocyte
mtDNA-CN
and
mtDNA4977
deletion
EOCAD.
The
included
118
patients
(99
men,
51.0
±
5.6
years)
angiographically
EOCAD
(≤60
150
healthy
controls
(94
49.8
5.8
years).
Quantitative
RT-PCR
was
used
quantify
rate.
group
had
higher
prevalence
male
gender
(p
<
0.001),
smoking
=
hypertension
diabetes
mellitus
0.04)
obesity
0.001)
than
controls.
lower
0.026).
Low
levels
were
significantly
0.004),
0.039),
hypercholesterolemia
0.001).
Increased
males
0.026)
hypercholesterolemic
ROC
curve
predicting
showed
an
AUC
0.902
(95%
CI
0.867-0.937,
p
0.762
0.691-0.834,
respectively.
Logistic
regression
analysis
adjusted
for
confounders
both
independent
significant
predictors
0.001
0.001,
respectively).
characterized
high
modifiable
factors
damage,
underscoring
need
more
efforts
reduce
burden
traditional
highlighting
potential
innovative
mitochondrial-targeted
therapies.
Language: Английский
The prevalence, patients' characteristics, and hyper-Lp(a)-emia risk factors in the polish population. The first results from the PMMHRI-Lp(a) registry
Progress in Cardiovascular Diseases,
Journal Year:
2024,
Volume and Issue:
86, P. 54 - 61
Published: Aug. 25, 2024
The
knowledge
on
the
prevalence
of
elevated
lipoprotein(a)
(Lp(a)),
patients'
characteristics,
and
nongenetic
risk
factors
is
scarce
in
some
regions
including
Poland,
largest
Central
Eastern
European
country.
Thus,
we
aimed
to
present
results
from
Lp(a)
registry
established
Poland's
2nd
largest,
supra-regional
hospital
-
Polish
Mother's
Memorial
Hospital
Research
Institute
(PMMHRI).
Language: Английский
New data allow to better understand the secrets of lipoprotein(a): is that for sure?
European Heart Journal Open,
Journal Year:
2024,
Volume and Issue:
4(5)
Published: Aug. 3, 2024
Language: Английский
Risk of adverse cardiovascular events based on common genetic variants in 8-year follow-up of the LIPIDOGEN2015 population using the polygenic risk score (PRS) - study design and methodology.
Archives of Medical Science,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 8, 2024
Introduction
Classical
risk
factors
such
as
hypertension,
hypercholesterolemia,
pre-diabetes,
diabetes
and
obesity
can
predict
adverse
cardiovascular
events,
but
they
are
less
prognostic
in
patients
age
<60
years.
Polygenic
scores
(PRS)
be
effective
predicting
coronary
events
younger
middle-aged
patients.
Our
main
aim
is
to
assess
the
utility
of
new
PRS
created
for
Polish
population
mortality
during
an
8-year
follow-up
a
nationwide
LIPIDOGEN2015
population.
Material
methods
All
DNA
samples
1779
were
genotyped
using
Infinium
Global
Screening
Array-24+
v3.0
Kit
microarrays.
The
amplified,
fragmented,
hybridized
BeadChips.
BeadChips
scanned
iScan
converted
genotypes
Genome
Studio
2.0.
Results
We
will
develop
based
on
marked
single
nucleotide
polymorphisms
(SNPs)
project's
studied
determine
analyzed
group's
death
due
diseases
(CVD)
data
obtained
from
8-years
patient-follow-up.
Based
developed
scale
biochemical
analyses,
we
effectiveness
lipid-lowering
therapy
with
statins
high
low
genetic
sudden
CVD
(secondary
endpoints).
Conclusions
scale,
combined
clinical
covariates,
facilitate
creation
algorithm
long-term
mortality.
This
enable
us
stratify
more
precisely,
which
may
result
earlier
implementation
lifestyle
changes
dietary
adjustments
potentially
initiate
pharmacotherapy
at-risk
individuals.
Language: Английский