The Journal of Cardiovascular Aging,
Journal Year:
2023,
Volume and Issue:
4(3)
Published: Dec. 13, 2023
Clonal
hematopoiesis
(CH)
is
a
prevalent
condition
that
results
from
somatic
mutations
in
hematopoietic
stem
cells.
When
these
occur
"driver"
genes,
they
can
potentially
confer
fitness
advantages
to
the
affected
cells,
leading
clonal
expansion.
While
most
expansions
of
mutant
cells
are
generally
considered
be
asymptomatic
since
do
not
impact
overall
blood
cell
numbers,
CH
carriers
face
long-term
risks
all-cause
mortality
and
age-associated
diseases,
including
cardiovascular
disease
hematological
malignancies.
considerable
research
has
focused
on
understanding
association
between
less
attention
been
given
exploring
regulatory
factors
contribute
expansion
driver
gene
clone.
This
review
focuses
environmental
stressors
inherited
genetic
risk
context
development.
A
better
how
development
will
facilitate
mechanistic
studies
lead
new
therapeutic
avenues
treat
individuals
with
this
condition.
GeroScience,
Journal Year:
2024,
Volume and Issue:
46(5), P. 5103 - 5132
Published: April 19, 2024
Cerebral
microhemorrhages
(CMHs,
also
known
as
cerebral
microbleeds)
are
a
critical
but
frequently
underestimated
aspect
of
small
vessel
disease
(CSVD),
bearing
substantial
clinical
consequences.
Detectable
through
sensitive
neuroimaging
techniques,
CMHs
reveal
an
extensive
pathological
landscape.
They
prevalent
in
the
aging
population,
with
multiple
often
being
observed
given
individual.
closely
associated
accelerated
cognitive
decline
and
increasingly
recognized
key
contributors
to
pathogenesis
vascular
impairment
dementia
(VCID)
Alzheimer's
(AD).
This
review
paper
delves
into
hypothesis
that
atherosclerosis,
age-related
large
disease,
extends
its
influence
microcirculation,
thereby
contributing
development
progression
CSVD,
specific
focus
on
CMHs.
We
explore
concept
continuum,
bridging
macrovascular
pathologies
like
atherosclerosis
microvascular
abnormalities
characteristic
CSVD.
posit
same
risk
factors
precipitating
vessels
(i.e.,
atherogenesis),
primarily
oxidative
stress
inflammatory
pathways,
similarly
instigate
aging.
Accelerated
leads
increased
fragility,
which
turn
predisposes
formation
The
presence
hypertension
amyloid
pathology
further
intensifies
this
process.
comprehensively
overview
current
body
evidence
supporting
interconnected
hypothesis.
Our
includes
examination
epidemiological
data,
provides
insights
prevalence
impact
context
Furthermore,
we
shared
mechanisms
between
aging,
atherogenesis,
particularly
focusing
how
these
intertwined
processes
contribute
genesis
By
highlighting
role
pathophysiology
CMHs,
seeks
enhance
understanding
CSVD
links
systemic
disorders.
aim
is
provide
could
inform
future
therapeutic
approaches
research
directions
realm
neurovascular
health.
Journal of Advanced Research,
Journal Year:
2024,
Volume and Issue:
unknown
Published: June 1, 2024
Atherosclerosis,
traditionally
considered
a
lipid-related
disease,
is
now
understood
as
chronic
inflammatory
condition
with
significant
global
health
implications.
This
review
aims
to
delve
into
the
complex
interactions
among
immune
cells,
cytokines,
and
cascade
in
atherosclerosis,
shedding
light
on
how
these
elements
influence
both
initiation
progression
of
disease.
draws
recent
clinical
research
elucidate
roles
key
macrophages,
T
endothelial
clonal
hematopoiesis
atherosclerosis
development.
It
focuses
cells
process
contribute
disease
progression,
particularly
through
inflammation-driven
processes
that
lead
plaque
formation
stabilization.
Macrophages
ingest
oxidized
low-density
lipoprotein
(oxLDL),
which
partially
converts
high-density
(HDL)
or
accumulates
lipid
droplets,
forming
foam
crucial
for
stability.
Additionally,
macrophages
exhibit
diverse
phenotypes
within
plaques,
pro-inflammatory
types
predominating
others
specializing
debris
clearance
at
rupture
sites.
The
involvement
CD4+
CD8+
promotes
macrophage
states,
suppresses
vascular
smooth
muscle
cell
proliferation,
enhances
instability.
nuanced
related
atherosclerotic
microenvironment
are
explored,
revealing
insights
cellular
molecular
pathways
fuel
inflammation.
also
addresses
advancements
imaging
biomarker
technology
enhance
our
understanding
progression.
Moreover,
it
points
out
limitations
current
treatment
highlights
potential
emerging
anti-inflammatory
strategies,
including
trials
agents
such
p38MAPK,
tumor
necrosis
factor
α
(TNF-α),
IL-1β,
their
preliminary
outcomes,
promising
effects
canakinumab,
colchicine,
IL-6R
antagonists.
explores
cutting-edge
interventions,
efficacy
preventing
alleviating
role
nanotechnology
delivering
drugs
more
effectively
safely.
Circulation Research,
Journal Year:
2024,
Volume and Issue:
135(9), P. 933 - 950
Published: Sept. 5, 2024
BACKGROUND:
Hypertension
incidence
increases
with
age
and
represents
one
of
the
most
prevalent
risk
factors
for
cardiovascular
disease.
Clonal
events
in
hematopoietic
system
resulting
from
somatic
mutations
driver
genes
are
elderly
individuals
who
lack
overt
hematologic
disorders.
This
condition
is
referred
to
as
age-related
clonal
hematopoiesis
(CH),
it
a
newly
recognized
factor
It
not
known
whether
CH
hypertension
causally
related
and,
if
so,
what
mechanistic
features.
METHODS:
A
murine
model
adoptive
bone
marrow
transplantation
was
employed
examine
interplay
between
Tet2
(ten-eleven
translocation
methylcytosine
dioxygenase
2)
hypertension.
RESULTS:
In
this
model,
subpressor
dose
Ang
II
(angiotensin
II)
resulted
elevated
systolic
diastolic
blood
pressure
early
1
day
after
challenge.
These
conditions
led
expansion
Tet2-deficient
proinflammatory
monocytes
progenitor
populations.
deficiency
promoted
renal
CCL5
(C-C
motif
ligand
5)
chemokine
expression
macrophage
infiltration
into
kidney.
Consistent
involvement,
myeloid
cells
when
mice
were
treated
II.
The
−/−
sodium
retention,
inflammasome
activation,
levels
IL
(interleukin)-1β
IL-18.
Analysis
transporters
indicated
NCC
(sodium-chloride
symporter)
NKCC2
(Na
+
-K
-Cl
−
cotransporter
activation
at
residues
Thr53
Ser105,
respectively.
Administration
NLRP3
(NLR
family
pyrin
domain
containing
3)
inhibitor
MCC950
reversed
hypertensive
state,
transporter
activation.
CONCLUSIONS:
Tet2-mediated
sensitizes
stimulus.
Mechanistically,
promotes
due
immune
cell
inflammasome,
consequences
on
retention.
data
indicate
that
carriers
TET2
could
be
development
modulators
useful
treating
patient
population.
GeroScience,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Oct. 15, 2024
Abstract
Aging
is
a
multifaceted
process
characterized
by
gradual
decline
in
physiological
function
and
increased
susceptibility
to
range
of
chronic
diseases.
Among
the
molecular
cellular
mechanisms
driving
aging,
genomic
instability
fundamental
hallmark,
contributing
mutation
load
genetic
heterogeneity
within
populations.
This
review
explores
role
aging
hematopoietic
system,
with
particular
focus
on
clonal
hematopoiesis
indeterminate
potential
(CHIP),
monoclonal
gammopathy
undetermined
significance
(MGUS),
B-cell
lymphocytosis
(MBL)
as
biomarkers.
CHIP
involves
expansion
stem
cells
somatic
mutations.
In
contrast,
MGUS
presence
plasma
producing
immunoglobulins,
while
MBL
proliferation
B
cells.
These
conditions
are
prevalent
population
serve
measurable
indicators
underlying
instability.
Studying
these
entities
offers
valuable
insights
into
which
mutations
accumulate
drive
evolution
providing
deeper
understanding
how
impacts
tissue
homeostasis.
summary,
system
serves
powerful
model
for
investigating
interplay
between
aging.
Incorporating
age-related
hematological
research,
alongside
other
biomarkers
such
epigenetic
clocks,
can
enhance
precision
predictive
power
biological
age
assessments.
provide
comprehensive
view
process,
facilitating
early
detection
diseases
hopefully
enabling
personalized
healthcare
strategies.
Blood Research,
Journal Year:
2025,
Volume and Issue:
60(1)
Published: March 13, 2025
Abstract
Clonal
hematopoiesis
(CH),
characterized
by
the
expansion
of
hematopoietic
stem
and
progenitor
cells
harboring
somatic
mutations,
has
emerged
as
a
significant
age-related
phenomenon
with
profound
implications
for
human
health.
While
initially
recognized
in
1960s,
recent
technological
advances
have
revealed
its
complex
nature
widespread
prevalence,
affecting
up
to
84%
individuals
aged
≥
70
years.
The
clinical
significance
CH
extends
beyond
well-established
role
precursor
hematological
malignancies,
encompassing
association
cardiovascular
diseases,
chronic
kidney
disease,
other
non-malignant
disorders.
This
comprehensive
review
synthesizes
current
understanding
CH,
focusing
on
genetic
molecular
mechanisms,
particularly
roles
commonly
mutated
genes
such
DNMT3A,
TET2,
ASXL1.
We
address
emerging
distinction
between
myeloid
lymphoid
their
differential
impacts
disease
progression,
interplay
inflammation.
Special
attention
is
given
newly
identified
determinants
clonal
rates
progression.
also
examines
revolutionary
concept
passenger-approximated
rate
utility
dynamics.
Furthermore,
we
discuss
therapeutic
strategies
targeting
inflammatory
pathways
potential
mitigating
CH-associated
complications.
By
integrating
findings
from
genetic,
molecular,
studies,
this
provides
framework
systemic
condition
highlights
promising
directions
interventions.
International Journal of Molecular Sciences,
Journal Year:
2025,
Volume and Issue:
26(7), P. 3252 - 3252
Published: April 1, 2025
Atherosclerosis,
a
chronic
inflammatory
disease
characterized
by
lipid
accumulation
and
immune
cell
infiltration,
is
linked
to
plaque
formation
cardiovascular
events.
While
traditionally
associated
with
metabolism
endothelial
dysfunction,
recent
research
highlights
the
roles
of
autophagy
clonal
hematopoiesis
(CH)
in
its
pathogenesis.
Autophagy,
cellular
process
crucial
for
degrading
damaged
components,
regulates
macrophage
homeostasis
inflammation,
both
which
are
pivotal
atherosclerosis.
In
macrophages,
influences
metabolism,
cytokine
regulation,
oxidative
stress,
helping
prevent
instability.
Defective
exacerbates
impairs
cholesterol
efflux,
accelerates
progression.
Additionally,
autophagic
processes
cells
smooth
muscle
further
contribute
atherosclerotic
pathology.
Recent
studies
also
emphasize
interplay
between
CH,
wherein
somatic
mutations
genes
like
TET2,
JAK2,
DNMT3A
drive
expansion
enhance
responses
plaques.
These
modify
function,
intensifying
environment
accelerating
Chaperone-mediated
(CMA),
selective
form
autophagy,
plays
critical
role
regulating
inflammation
pro-inflammatory
cytokines
oxidized
low-density
lipoprotein
(ox-LDL).
Impaired
CMA
activity
leads
these
substrates,
activating
NLRP3
inflammasome
worsening
inflammation.
Preclinical
suggest
that
pharmacologically
may
mitigate
atherosclerosis
animal
models,
reduced
instability
increases
This
review
importance
regulation
focusing
on
formation,
contributions
CH.
Building
upon
current
advances,
we
propose
hypothesis
programmed
death,
intrinsic
axis
modulates
fundamental
functions
playing
complex
development
Understanding
mechanisms
offers
potential
therapeutic
strategies
targeting
reduce
burden
disease.
