bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 15, 2025
Age-related
macular
degeneration
(AMD),
characterized
by
pathologic
choroidal
neovascularization
(CNV),
is
a
leading
cause
of
vision
loss
in
the
elderly.
Vascular
endothelial
growth
factor
A
(VEGFa)
antagonists
can
prevent
acute
loss,
but
high
treatment
burden
and
efficacy
with
chronic
therapy
highlight
need
to
explore
alternative
mechanisms.
Recently,
microRNA-34a
(miR-34a)
has
emerged
as
key
regulator
aging
age-related
diseases,
its
role
neovascular
AMD
unclear.
In
an
injury-induced
murine
CNV
model,
we
discovered
miR-34a
promoted
pathological
angiogenesis,
without
altering
expression
Vegfa
or
receptor
Kdr,
canonical
regulators
CNV.
Mechanistically,
directly
targets
inhibits
transcription
KLF2
thereby
upregulating
pro-angiogenic
factors
CXCR4
CXCL12.
Finally,
show
exacerbates
aged
mice
expressed
lesions
excised
from
wet
patients.
These
findings
establish
causal
link
between
AMD.
Identification
molecular
mechanism
involved
pathogenesis
prevalent
debilitating
ocular
disease.
Abstract
Background
The
global
population
of
older
individuals
is
growing,
and
ageing
a
key
risk
factor
for
atherosclerotic
cardiovascular
diseases.
Abnormal
accumulation
senescent
cells
can
cause
potentially
deleterious
effects
on
the
organism
with
age.
As
vital
marker
cellular
senescence,
senescence-associated
secretory
phenotype
(SASP)
novel
mechanism
to
link
senescence
atherosclerosis.
Main
body
In
this
review,
we
concretely
describe
characteristics
SASP
its
regulation
mechanisms.
Importantly,
provide
perspectives
how
promote
from
different
types
have
roles
in
atherosclerosis
progression.
significant
mediator
harmful
cells,
it
play
pro-atherogenic
role
by
producing
inflammation
immune
dysfunction.
Furthermore,
deliver
signals
surrounding
vascular
gradually
contributing
development
Finally,
focus
variety
therapeutic
strategies
aimed
reduce
burden
elderly
targeting
inhibiting
regulatory
mechanisms
SASP.
Conclusion
This
review
systematically
summarizes
multiple
contribute
exploration
new
opportunities.
Frontiers in Cardiovascular Medicine,
Год журнала:
2022,
Номер
8
Опубликована: Янв. 27, 2022
Cardiovascular
diseases
(CVDs)
are
still
the
main
cause
of
morbidity
and
mortality
worldwide
include
a
group
disorders
varying
from
vasculature,
myocardium,
arrhythmias
cardiac
development.
MicroRNAs
(miRs)
endogenous
non-coding
RNAs
with
18-23
nucleotides
that
regulate
gene
expression.
The
miR-34
family,
including
miR-34a/b/c,
plays
vital
role
in
regulation
myocardial
physiology
pathophysiological
processes.
Recently,
miR-34a
has
been
implicated
cardiovascular
fibrosis,
dysfunction
related
as
an
essential
regulator.
Interestingly,
there
is
pivotal
link
among
miR-34a,
Smad4/TGF-β1
signaling.
Notably,
both
loss-of-function
gain-of-function
approaches
identified
critical
roles
apoptosis,
autophagy,
inflammation,
senescence
remodeling
by
modulating
multifunctional
signaling
pathways.
In
this
article,
we
focus
on
current
understanding
biogenesis,
its
biological
effects
implications
for
pathologies
infarction,
heart
failure,
ischaemia
reperfusion
injury,
cardiomyopathy,
atherosclerosis,
hypertension
atrial
fibrillation.
Thus,
further
will
aid
development
effective
interventions.
Targeting
emerged
potential
therapeutic
target
diseases.
Current Atherosclerosis Reports,
Год журнала:
2022,
Номер
24(6), С. 483 - 492
Опубликована: Апрель 11, 2022
Abstract
Purpose
of
the
Review
In
this
review,
we
summarize
current
insights
into
versatile
roles
endothelial
cells
in
atherogenesis.
Recent
Findings
The
vascular
endothelium
represents
first
barrier
that
prevents
entry
lipoproteins
and
leukocytes
vessel
wall,
thereby
controlling
two
key
events
pathogenesis
atherosclerosis.
Disturbance
homeostasis
increases
permeability,
inflammation,
cellular
trans-differentiation,
which
not
only
promotes
build-up
atherosclerotic
plaques
but
is
also
involved
life-threatening
thromboembolic
complications
such
as
plaque
rupture
erosion.
focus
on
recent
findings
lipoprotein
transport,
transitions,
function.
Summary
By
using
cutting-edge
technologies
single-cell
sequencing,
epigenetics,
cell
fate
mapping,
novel
regulatory
mechanisms
phenotypes
have
been
discovered,
challenged
established
concepts
activation,
led
to
a
different
view
disease.
Aging
of
the
vasculature,
which
is
integral
to
functioning
literally
all
human
organs,
serves
as
a
fundamental
physiological
basis
for
age-related
alterations
well
shared
etiological
mechanism
various
chronic
diseases
prevalent
in
elderly
population.
China,
home
world's
largest
aging
population,
faces
an
escalating
challenge
addressing
prevention
and
management
these
conditions.
To
meet
this
challenge,
Biomarker
Consortium
China
has
developed
expert
consensus
on
biomarkers
vascular
(VA)
by
synthesizing
literature
insights
from
scientists
clinicians.
This
provides
comprehensive
assessment
associated
with
VA
presents
systemic
framework
classify
them
into
three
dimensions:
functional,
structural,
humoral.
Within
each
dimension,
panel
recommends
most
clinically
relevant
biomarkers.
For
functional
domain,
reflecting
stiffness
endothelial
function
are
highlighted.
The
structural
dimension
encompasses
metrics
structure,
microvascular
distribution.
Additionally,
proinflammatory
factors
emphasized
humoral
dimension.
aim
establish
foundation
assessing
extent
conducting
research
related
VA,
ultimate
goal
improving
health
globally.
Journal of Diabetes & Metabolic Disorders,
Год журнала:
2025,
Номер
24(1)
Опубликована: Март 3, 2025
Obesity
and
osteoporosis
are
interrelated
global
health
challenges,
both
characterized
by
dysregulated
bone
metabolism
adipose
tissue
dynamics,
contributing
to
increased
fracture
risk
systemic
complications.
Emerging
evidence
underscores
the
pivotal
role
of
microRNAs
(miRNAs)
as
regulatory
molecules
governing
intricate
balance
between
adipogenesis
osteogenesis,
thereby
providing
a
molecular
link
these
two
conditions.
Both
disorders
alterations
in
which
increase
fractures
Recent
advancements
biology
have
identified
miRNAs
crucial
regulators
disorders,
influencing
differentiation
marrow
mesenchymal
stem
cells
(BMSCs)
into
osteoblasts
(bone-forming
cells)
adipocytes
(fat-storing
cells).
This
review
provides
comprehensive
analysis
dual
modulating
osteogenesis
adipogenesis,
with
particular
focus
on
their
implications
disease
progression
therapeutic
strategies.
It
first
explores
how
specific
regulate
critical
energy
metabolism,
inflammation,
remodeling
pathways.
By
integrating
insights
from
biology,
endocrinology,
clinical
practice,
highlights
potential
miRNA-based
interventions.
Targeting
could
restore
offering
innovative
approaches
simultaneously
address
obesity
osteoporosis.
These
proposed
strategies
hold
promise
for
improving
patient
outcomes
mitigating
risk,
enhancing
density,
addressing
metabolic
dysfunctions
associated
obesity.
Ultimately,
future
research
should
translating
applications
develop
effective
therapies
that
tackle
complex
interplay
prevalent
Journal of Orthopaedic Surgery and Research,
Год журнала:
2023,
Номер
18(1)
Опубликована: Март 13, 2023
Osteoarthritis
(OA)
is
the
most
common
degenerative
disease
in
joints
among
elderly
patients.
Senescence
deeply
involved
pathogenesis
of
osteoarthritis.
Metformin
widely
used
as
first-line
drug
for
Type
2
diabetes
mellitus
(T2DM),
and
has
great
potential
treatment
other
aging-related
disorders,
including
OA.
However,
role
metformin
OA
not
fully
elucidated.
Therefore,
our
aim
here
was
to
investigate
effects
on
human
chondrocytes.After
treatment,
expression
level
microRNA-34a
SIRT1
chondrocyte
were
detected
with
quantitative
real-time
PCR
immunofluorescence
staining.
Then,
mimic
small
interfering
RNA
(siRNA)
against
(siRNA-SIRT1)
transfected
into
chondrocyte.
Senescence-associated
β-galactosidase
(SA-β-gal)
staining
performed
assess
senescence.
Chondrocyte
viability
illustrated
MTT
colony
formation
assays.
Western
blot
conducted
detect
P16,
IL-6,
matrix
metalloproteinase-13
(MMP-13),
Collagen
type
II
(COL2A1)
Aggrecan
(ACAN).We
found
that
(1
mM)
inhibited
while
promoted
chondrocytes.
Both
miR-34a
mimics
siRNA
SA-β-gal
assay
confirmed
reduced
SA-β-gal-positive
rate
chondrocytes,
transfection
or
siRNA-SIRT1
reversed
it.
showed
accelerated
proliferation,
weakened
this
effect.
Furthermore,
results
from
western
demonstrated
suppressed
senescence-associated
protein
proinflammatory
cytokine
IL-6
catabolic
gene
MMP-13
elevated
anabolic
proteins
such
Aggrecan,
which
could
be
attenuated
by
mimics.Overall,
data
suggest
regulates
senescence
proliferation
through
microRNA-34a/SIRT1
pathway,
indicating
it
a
novel
strategy
treatment.
