Open Life Sciences,
Год журнала:
2024,
Номер
19(1)
Опубликована: Янв. 1, 2024
In
this
study,
we
integrated
transcriptomic
and
metabolomic
analyses
to
achieve
a
comprehensive
understanding
of
the
underlying
mechanisms
diabetic
cardiomyopathy
(DCM)
in
rat
model.
Functional
molecular
characterizations
revealed
significant
cardiac
injury,
dysfunction,
ventricular
remodeling
DCM.
A
thorough
analysis
global
changes
genes
metabolites
showed
that
amino
acid
metabolism,
especially
breakdown
branched-chain
acids
(BCAAs)
such
as
valine,
leucine,
isoleucine,
is
highly
dysregulated.
Furthermore,
study
identified
transcription
factor
Gata3
predicted
negative
regulator
gene
encoding
key
enzyme
for
BCAA
degradation.
These
findings
suggest
disruption
degradation
critical
characteristic
myocardial
damage
indicate
potential
role
dysregulation
metabolism
context
Nature Communications,
Год журнала:
2022,
Номер
13(1)
Опубликована: Ноя. 14, 2022
Heart
failure
is
a
leading
cause
of
cardiovascular
morbidity
and
mortality.
However,
the
contribution
common
genetic
variation
to
heart
risk
has
not
been
fully
elucidated,
particularly
in
comparison
other
cardiometabolic
traits.
We
report
multi-ancestry
genome-wide
association
study
meta-analysis
all-cause
including
up
115,150
cases
1,550,331
controls
diverse
ancestry,
identifying
47
loci.
also
perform
multivariate
studies
that
integrate
with
related
cardiac
magnetic
resonance
imaging
endophenotypes,
61
Gene-prioritization
analyses
colocalization
transcriptome-wide
identify
known
previously
unreported
candidate
cardiomyopathy
genes
cellular
processes,
which
we
validate
gene-expression
profiling
failing
healthy
human
hearts.
Colocalization,
gene
expression
profiling,
Mendelian
randomization
provide
convergent
evidence
for
roles
BCKDHA
circulating
branch-chain
amino
acids
structure.
Finally,
proteome-wide
identifies
9
proteins
associated
or
quantitative
These
highlight
similarities
differences
among
implicate
pathogenesis
failure,
may
represent
treatment
targets.
Journal of Translational Medicine,
Год журнала:
2023,
Номер
21(1)
Опубликована: Фев. 1, 2023
Diabetic
cardiomyopathy
(DCM)
is
one
of
the
common
cardiovascular
complications
diabetes
and
a
leading
cause
death
in
diabetic
patients.
Mitochondrial
metabolism
immune-inflammation
are
key
for
DCM
pathogenesis,
but
their
crosstalk
remains
an
open
issue.
This
study
explored
separate
roles
mitochondrial
immune
microenvironment
with
bioinformatics.DCM
chip
data
(GSE4745,
GSE5606,
GSE6880)
were
obtained
from
NCBI
GEO,
while
gene
downloaded
MitoCarta3.0
database.
Differentially
expressed
genes
(DEGs)
screened
by
GEO2R
processed
GSEA,
GO
KEGG
pathway
analyses.
Mitochondria-related
DEGs
(MitoDEGs)
obtained.
A
PPI
network
was
constructed,
hub
MitoDEGs
closely
linked
to
or
heart
failure
identified
CytoHubba,
MCODE
CTD
scores.
Transcription
factors
target
miRNAs
predicted
Cytoscape
miRWalk
database,
respectively,
regulatory
established.
The
infiltration
pattern
analyzed
ImmuCellAI,
relationship
between
abundance
investigated
using
Spearman
method.
rat
model
established
validate
expression
cardiac
function.MitoDEGs
significantly
enriched
pathways
involved
metabolism,
immunoregulation,
collagen
synthesis.
Nine
Immune
analysis
revealed
increased
B
cells
decreased
DCs
DCM.
demonstrated
that
positively
associated
pro-inflammatory
cells,
negatively
anti-inflammatory
cells.
In
animal
experiment,
4
(Pdk4,
Hmgcs2,
Decr1,
Ivd)
showed
trend
consistent
bioinformatics
result.
Additionally,
up-regulation
Pdk4,
Decr1
down-regulation
Ivd
distinctly
reduced
function.This
unraveled
interaction
DCM,
providing
new
insights
into
research
on
potential
pathogenesis
exploration
novel
targets
medical
interventions.
Circulation Research,
Год журнала:
2022,
Номер
130(12), С. 1965 - 1993
Опубликована: Июнь 9, 2022
As
a
muscular
pump
that
contracts
incessantly
throughout
life,
the
heart
must
constantly
generate
cellular
energy
to
support
contractile
function
and
fuel
ionic
pumps
maintain
electrical
homeostasis.
Thus,
mitochondrial
metabolism
of
multiple
metabolic
substrates
such
as
fatty
acids,
glucose,
ketones,
lactate
is
essential
ensuring
an
uninterrupted
supply
ATP.
Multiple
pathways
converge
myocardial
The
regulation
these
cardiac
has
been
intensely
studied
for
many
decades.
Rapid
adaptation
mediating
stress,
dysregulation
contributes
pathophysiology
occurs
in
failure
disorders
diabetes.
reflects
complex
interactions
cell-specific
regulatory
pathways,
neurohumoral
signals,
changes
substrate
availability
circulation.
Significant
advances
have
made
ability
study
heart,
animal
models
played
central
role
contributing
this
knowledge.
This
review
will
summarize
describe
their
contribution
maintaining
health
disease.
lessons
learned
from
with
altered
systemic
those
which
specific
genetically
within
heart.
relationship
between
intrinsic
extrinsic
regulators
how
informed
by
be
discussed.
Journal of the American Heart Association,
Год журнала:
2020,
Номер
9(22)
Опубликована: Ноя. 11, 2020
Abstract
Hypertrophic
cardiomyopathy
(HCM)
is
the
most
common
inherited
and
characterized
by
asymmetric
septal
thickening
diastolic
dysfunction.
More
than
1500
mutations
in
genes
encoding
sarcomere
proteins
are
associated
with
HCM.
However,
genotype‐phenotype
relationship
HCM
incompletely
understood
involves
modification
additional
disease
hits.
Recent
cohort
studies
identify
obesity
as
a
major
adverse
modifier
of
penetrance,
severity,
clinical
course.
In
this
review,
we
provide
an
overview
these
findings.
Moreover,
explore
putative
mechanisms
underlying
obesity‐induced
sensitization
aggravation
phenotype.
We
hypothesize
obesity‐related
stressors
to
impact
on
cardiomyocyte
structure,
metabolism,
homeostasis.
These
may
impair
cardiac
function
directly
acting
primary
mutation‐induced
myofilament
defects
independently
adding
total
burden.
Last,
address
important
pharmacological
implications
involvement
modification.
Frontiers in Aging Neuroscience,
Год журнала:
2024,
Номер
16
Опубликована: Апрель 10, 2024
We
aimed
to
examine
the
association
between
blood
levels
of
Branched-chain
amino
acids
(BCAAs)
-
specifically
isoleucine,
leucine,
and
valine
susceptibility
three
neurodegenerative
disorders:
dementia,
Alzheimer's
disease
(AD),
Parkinson's
(PD).
Nutrients,
Год журнала:
2024,
Номер
16(12), С. 1972 - 1972
Опубликована: Июнь 20, 2024
Branched-chain
amino
acids
(BCAAs),
comprising
leucine
(Leu),
isoleucine
(Ile),
and
valine
(Val),
are
essential
nutrients
vital
for
protein
synthesis
metabolic
regulation
via
specialized
signaling
networks.
Their
association
with
cardiovascular
diseases
(CVDs)
has
become
a
focal
point
of
scientific
debate,
emerging
evidence
suggesting
both
beneficial
detrimental
roles.
This
review
aims
to
dissect
the
multifaceted
relationship
between
BCAAs
health,
exploring
molecular
mechanisms
clinical
implications.
Elevated
BCAA
levels
have
also
been
linked
insulin
resistance
(IR),
type
2
diabetes
mellitus
(T2DM),
inflammation,
dyslipidemia,
which
well-established
risk
factors
CVD.
Central
these
processes
key
pathways
such
as
mammalian
target
rapamycin
(mTOR)
signaling,
nuclear
factor
kappa-light-chain-enhancer
activate
B
cells
(NF-κB)-mediated
oxidative
stress.
Additionally,
interplay
metabolism
gut
microbiota,
particularly
production
metabolites
like
trimethylamine-N-oxide
(TMAO),
adds
another
layer
complexity.
Contrarily,
some
studies
propose
that
may
cardioprotective
effects
under
certain
conditions,
contributing
muscle
maintenance
health.
critically
evaluates
evidence,
addressing
biological
basis
signal
transduction
mechanism,
discusses
potential
act
biomarkers
versus
active
mediators
pathology.
By
presenting
balanced
analysis,
this
seeks
clarify
contentious
roles
in
CVD,
providing
foundation
future
research
therapeutic
strategies
required
because
rising
prevalence,
incidence,
total
burden
CVDs.
