Atrial Fibrosis in Atrial Fibrillation: Mechanistic Insights, Diagnostic Challenges, and Emerging Therapeutic Targets
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
26(1), P. 209 - 209
Published: Dec. 30, 2024
Atrial
fibrosis
is
a
hallmark
of
atrial
cardiomyopathy
and
plays
pivotal
role
in
the
pathogenesis
fibrillation
(AF),
contributing
to
its
onset
progression.
The
mechanisms
underlying
are
multifaceted,
involving
stretch-induced
fibroblast
activation,
oxidative
stress,
inflammation,
coagulation
pathways.
Variations
types-reactive
replacement
fibrosis-are
influenced
by
patient-specific
factors
such
as
age,
sex,
comorbidities,
complicating
therapeutic
approaches.
heterogeneity
leads
distinct
electrophysiological
abnormalities
that
promote
AF
via
reentrant
activity
enhanced
automaticity
mechanisms.
Despite
advancements
imaging,
late
gadolinium
enhancement
CMR
electroanatomical
mapping,
challenges
accurately
quantifying
persist.
Emerging
strategies
include
antifibrotic
agents
targeting
renin-angiotensin-aldosterone
system,
novel
pathways
like
TGF-β
signaling,
cardio-metabolic
drugs
SGLT2
inhibitors
GLP-1
receptor
agonists.
Innovative
interventions,
including
microRNA
modulation
lipid
nanoparticle-based
therapies,
show
promise
but
require
validation.
Knowledge
gaps
remain
correlating
clinical
outcomes
with
patterns
optimizing
diagnostic
tools.
Future
research
should
focus
on
precise
phenotyping,
integrating
advanced
imaging
molecular
biomarkers,
conducting
robust
trials
evaluate
therapies'
efficacy
reducing
burden
related
complications.
Language: Английский
Hypoxic extracellular vesicles from hiPSCs protect cardiomyocytes from oxidative damage by transferring antioxidant proteins and enhancing Akt/Erk/NRF2 signaling
Cell Communication and Signaling,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: July 9, 2024
Abstract
Background
Stem
cell-derived
extracellular
vesicles
(EVs)
are
an
emerging
class
of
therapeutics
with
excellent
biocompatibility,
bioactivity
and
pro-regenerative
capacity.
One
the
potential
targets
for
EV-based
medicines
cardiovascular
diseases
(CVD).
In
this
work
we
used
EVs
derived
from
human
induced
pluripotent
stem
cells
(hiPSCs;
hiPS-EVs)
cultured
under
different
oxygen
concentrations
(21,
5
3%
O
2
)
to
dissect
molecular
mechanisms
responsible
cardioprotection.
Methods
were
isolated
by
ultrafiltration
combined
size
exclusion
chromatography
(UF
+
SEC),
followed
characterization
nanoparticle
tracking
analysis,
atomic
force
microscopy
(AFM)
Western
blot
methods.
Liquid
tandem
mass
spectrometry
coupled
bioinformatic
analyses
identify
differentially
enriched
proteins
in
various
conditions.
We
directly
compared
cardioprotective
effects
these
oxygen-glucose
deprivation/reoxygenation
(OGD/R)
model
cardiomyocyte
(CM)
injury.
Using
advanced
biology,
fluorescence
microscopy,
spectroscopy
bioinformatics
techniques,
investigated
intracellular
signaling
pathways
involved
regulation
cell
survival,
apoptosis
antioxidant
response.
The
direct
effect
on
NRF2-regulated
was
evaluated
CMs
following
NRF2
inhibition
ML385.
Results
demonstrate
that
hiPS-EVs
physiological
hypoxia
at
5%
(EV-H5)
exert
enhanced
cytoprotective
function
towards
damaged
other
tested
conditions
(normoxia;
EV-N
;
EV-H3).
This
resulted
higher
phosphorylation
rates
Akt
kinase
recipient
after
transfer,
modulation
AMPK
activity
reduced
apoptosis.
Furthermore,
provide
evidence
improved
calcium
sustained
contractility
treated
EV-H5
using
AFM
measurements.
Mechanistically,
our
revealed
associated
pathway
regulated
NRF2.
regard,
increased
nuclear
translocation
protein
its
transcription
upon
OGD/R.
contrast,
ML385
abolished
protective
CMs.
Conclusions
work,
a
superior
EV-H3.
Such
most
effective
restoring
redox
balance
stressed
CMs,
preserving
their
contractile
preventing
death.
Our
data
support
use
hypoxia,
as
cell-free
regenerative
properties
treatment
cardiac
diseases.
Language: Английский
Translation of pathophysiological mechanisms of atrial fibrosis into new diagnostic and therapeutic approaches
Nature Reviews Cardiology,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 23, 2024
Language: Английский
Exosomal miR‐107 Derived From Cigarette Smoking‐Exposed Bronchial Epithelial Cells Aggravates Acute Lung Injury by Polarizing Macrophage to Proinflammatory Phenotype
Xin Ni,
No information about this author
Yufeng Lv,
No information about this author
Lei Han
No information about this author
et al.
Journal of Biochemical and Molecular Toxicology,
Journal Year:
2025,
Volume and Issue:
39(2)
Published: Feb. 1, 2025
ABSTRACT
Exosomes
are
critical
mediators
of
intercellular
crosstalk
and
play
significant
roles
in
the
progression
various
diseases
including
acute
lung
injury
(ALI).
However,
specific
role
exosomes
ALI
remains
largely
unexplored.
In
investigation,
we
demonstrated
that
released
from
cigarette
smoke
extract
(CSE)‐exposed
bronchial
epithelial
cells
(BEAS‐2B)
facilitated
M1
macrophage
polarization.
Notably,
CSE
exposure
enhanced
production
miR‐107
within
these
exosomes.
Inhibition
markedly
reversed
polarization
inflammatory
responses
vitro
ameliorated
vivo.
Furthermore,
exosomal
was
found
to
downregulate
KLF4,
thereby
promoting
inflammation
macrophages.
Collectively,
findings
demonstrate
CSE‐exposed
BEAS‐2B
could
induce
via
transmitting
miR‐107,
eventually
ultimately
contributing
ALI,
indicating
a
potential
therapeutic
strategy
for
ALI.
Language: Английский
Small extracellular vesicles associated miRNA in myocardial fibrosis
Biochemical and Biophysical Research Communications,
Journal Year:
2024,
Volume and Issue:
727, P. 150336 - 150336
Published: June 30, 2024
Myocardial
fibrosis
involves
the
loss
of
cardiomyocytes,
myocardial
fibroblast
proliferation,
and
a
reduction
in
angiogenesis,
ultimately
leading
to
heart
failure,
Given
its
significant
implications,
it
is
crucial
explore
novel
therapies
for
fibrosis.
Recently
one
emerging
avenue
has
been
use
small
extracellular
vesicles
(sEV)-carried
miRNA.
In
this
review,
we
summarize
regulatory
role
sEV-carried
miRNA
We
explored
not
only
potential
diagnostic
value
circulating
as
biomarkers
disease
but
also
therapeutic
implications
derived
from
various
cellular
sources
applications
modified
sEV.
This
exploration
paramount
researchers
striving
develop
innovative,
cell-free
drug
candidates
management
Language: Английский
Extracellular vesicle therapeutics for cardiac repair
Yilan Hu,
No information about this author
Weihang Zhang,
No information about this author
Shah R. Ali
No information about this author
et al.
Journal of Molecular and Cellular Cardiology,
Journal Year:
2024,
Volume and Issue:
199, P. 12 - 32
Published: Nov. 26, 2024
Language: Английский
New Insights into the Role of Mild Hypoxia in Regulating Neural Stem Cell Characteristics
Jianjun Guo,
No information about this author
Ruibin Su,
No information about this author
Haitao Wu
No information about this author
et al.
Stem Cells and Development,
Journal Year:
2024,
Volume and Issue:
33(13-14), P. 333 - 342
Published: May 16, 2024
The
proliferation
of
neural
stem
cells
(NSCs)
is
precisely
regulated
by
extracellular
environmental
factors.
In
situ
hypoxia,
one
the
key
factors
involved
in
regulation
NSC
characteristics,
has
attracted
increasing
amounts
attention.
Numerous
studies
have
demonstrated
that
hypoxia
can
significantly
promote
formation
neurospheres
and
NSCs
vitro
intermittent
endogenous
vivo.
this
article,
effects
different
concentrations
oxygen
on
differentiation
both
vivo
are
reviewed,
potential
applications
hypoxia-preconditioned
NSCs,
as
well
research
progress
challenges
treatment
central
nervous
system
diseases,
further
summarized.
Here,
critical
role
neurogenesis
emphasized,
insights
into
use
to
regulate
characteristics
provided.
Language: Английский
Innovative Therapeutic Strategies for Myocardial Infarction Across Various Stages: Non-Coding RNA and Stem Cells
Bingqi Zhuang,
No information about this author
Chongning Zhong,
No information about this author
Yuting Ma
No information about this author
et al.
International Journal of Molecular Sciences,
Journal Year:
2024,
Volume and Issue:
26(1), P. 231 - 231
Published: Dec. 30, 2024
Myocardial
infarction
(MI)
is
a
highly
challenging
and
fatal
disease,
with
diverse
challenges
arising
at
different
stages
of
its
progression.
As
such,
non-coding
RNAs
(ncRNAs),
which
can
broadly
regulate
cell
fate,
stem
cells
multi-differentiation
potential
are
emerging
as
novel
therapeutic
approaches
for
treating
MI
across
various
stages.
NcRNAs,
including
microRNAs
(miRNAs)
long
(LncRNAs),
directly
participate
in
regulating
intracellular
signaling
pathways,
influence
cardiac
angiogenesis,
promote
the
repair
infarcted
myocardium.
Currently,
commonly
used
medicine,
such
mesenchymal
(MSCs)
induced
pluripotent
(iPSCs),
differentiate
into
human
types
without
ethical
concerns.
When
combined
ncRNAs,
these
more
effectively
induce
directed
differentiation,
angiogenesis
heart,
replenish
normal
cells.
Additionally,
cell-derived
exosomes,
contain
improve
myocardial
damage
region
through
paracrine
mechanisms.
However,
our
understanding
specific
roles
mechanisms
cells,
exosomes
secreted
by
during
remains
limited.
Therefore,
this
review
systematically
categorizes
MI,
aiming
to
summarize
direct
regulatory
effects
ncRNAs
on
an
myocardium
points
disease
Moreover,
it
explores
therapy
exosome
complex
pathological
evolution
process.
The
objective
was
provide
insights
strategies
open
new
research
directions
application
field
repair.
Language: Английский