Methodist DeBakey Cardiovascular Journal,
Journal Year:
2023,
Volume and Issue:
19(5), P. 16 - 25
Published: Jan. 1, 2023
Cardiovascular
diseases
are
the
number
one
cause
of
death
worldwide
and
in
United
States
(US).
frequently
progress
to
end-stage
heart
failure,
curative
therapies
extremely
limited.
Intense
interest
has
focused
on
deciphering
cascades
networks
that
govern
cardiomyocyte
proliferation
regeneration
injured
heart.
For
example,
studies
have
shown
lower
organisms
such
as
adult
newt
zebrafish
capacity
completely
regenerate
their
with
restoration
function.
Similarly,
neonatal
mouse
pig
also
able
myocardium
due
from
preexisting
cardiomyocytes.
Using
these
animal
models
transcriptome
analyses,
efforts
definition
factors
signaling
pathways
can
reactivate
induce
mammalian
These
discoveries
potential
define
novel
promote
repair
injured,
npj Regenerative Medicine,
Journal Year:
2025,
Volume and Issue:
10(1)
Published: Jan. 22, 2025
Myocardial
infarction
(MI)
causes
the
loss
of
millions
cardiomyocytes,
and
current
treatments
do
not
address
this
root
issue.
New
therapies
focus
on
stimulating
cardiomyocyte
division
in
adult
heart,
inspired
by
regenerative
capacities
lower
vertebrates
neonatal
mice.
This
review
explores
strategies
for
heart
regeneration,
offers
insights
into
proliferation,
evaluates
vivo
models,
discusses
integrating
vitro
human
cardiac
models
to
advance
regeneration
research.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: Jan. 2, 2025
Energy
deprivation
and
metabolic
rewiring
of
cardiomyocytes
are
widely
recognized
hallmarks
heart
failure.
Here,
we
report
that
HEY2
(a
Hairy/Enhancer-of-split-related
transcriptional
repressor)
is
upregulated
in
hearts
patients
with
dilated
cardiomyopathy.
Induced
Hey2
expression
zebrafish
or
mammalian
impairs
mitochondrial
respiration,
accompanied
by
elevated
ROS,
resulting
cardiomyocyte
apoptosis
Conversely,
depletion
adult
mouse
enhances
the
oxidation
genes
cardiac
function.
Multifaceted
genome-wide
analyses
reveal
enriches
at
promoters
known
to
regulate
metabolism
(including
Ppargc1,
Esrra
Cpt1)
colocalizes
HDAC1
effectuate
histone
deacetylation
repression.
Consequently,
restoration
PPARGC1A/ESRRA
Hey2-
overexpressing
human
cardiomyocyte-like
cells
rescues
deficits
bioenergetics.
Knockdown
protects
against
doxorubicin-induced
dysfunction.
These
studies
an
evolutionarily
conserved
HEY2/HDAC1-Ppargc1/Cpt
module
controls
energy
preserve
Mitochondrial
dysfunction
contributes
pathogenesis
during
Here
authors
repressor
regulates
function
hearts.
Journal of Molecular and Cellular Cardiology,
Journal Year:
2023,
Volume and Issue:
187, P. 38 - 50
Published: Dec. 30, 2023
The
heart
undergoes
a
dynamic
maturation
process
following
birth,
in
response
to
wide
range
of
stimuli,
including
both
physiological
and
pathological
cues.
This
entails
substantial
re-programming
mitochondrial
energy
metabolism
coincident
with
the
emergence
specialized
structural
contractile
machinery
meet
demands
adult
heart.
Many
components
this
program
revert
more
"fetal"
format
during
development
cardiac
hypertrophy
failure.
In
review,
emphasis
is
placed
on
recent
progress
our
understanding
transcriptional
control
maturation,
encompassing
results
studies
spanning
from
vivo
models
cardiomyocytes
derived
human
stem
cells.
potential
applications
current
state
knowledge
new
translational
avenues
aimed
at
treatment
failure
also
addressed.
Basic Research in Cardiology,
Journal Year:
2024,
Volume and Issue:
119(3), P. 349 - 369
Published: April 29, 2024
Heart
failure
continues
to
be
a
significant
global
health
concern,
causing
substantial
morbidity
and
mortality.
The
limited
ability
of
the
adult
heart
regenerate
has
posed
challenges
in
finding
effective
treatments
for
cardiac
pathologies.
While
various
medications
surgical
interventions
have
been
used
improve
function,
they
are
not
able
address
extensive
loss
functioning
cardiomyocytes
that
occurs
during
injury.
As
result,
there
is
growing
interest
understanding
how
cell
cycle
regulated
exploring
potential
stimulating
cardiomyocyte
proliferation
as
means
promoting
regeneration.
This
review
aims
provide
an
overview
current
knowledge
on
regulation
mechanisms
underlying
cases
failure,
while
also
highlighting
established
novel
therapeutic
strategies
targeting
this
area
treatment
purposes.
Nature Biomedical Engineering,
Journal Year:
2024,
Volume and Issue:
8(9), P. 1124 - 1141
Published: May 2, 2024
The
adenovirus-mediated
somatic
transfer
of
the
embryonic
T-box
transcription
factor
18
(TBX18)
gene
can
convert
chamber
cardiomyocytes
into
induced
pacemaker
cells.
However,
translation
therapeutic
TBX18-induced
cardiac
pacing
faces
safety
challenges.
Here
we
show
that
myocardial
expression
synthetic
TBX18
mRNA
in
animals
generates
de
novo
and
limits
innate
inflammatory
immune
responses.
In
rats,
intramyocardially
injected
remained
localized,
whereas
direct
injection
an
adenovirus
carrying
a
reporter
resulted
diffuse
substantial
spillover
to
liver,
spleen
lungs.
Transient
rats
led
automaticity
properties
and,
compared
with
adenovirus,
reductions
genes
activated
macrophage
populations.
rodent
clinically
relevant
porcine
models
complete
heart
block,
provided
rate-adaptive
for
one
month
strongly
correlated
animal's
sinus
rhythm
physical
activity.
may
aid
development
biological
pacemakers.
Advanced Science,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 3, 2025
The
adult
mammalian
heart
has
limited
regenerative
capacity
to
replace
lost
tissue
after
a
major
injury.
Forkhead
box
P1
(Foxp1)
regulates
embryonic
cardiomyocyte
proliferation
and
development.
However,
whether
Foxp1
participates
in
postnatal-injury
regeneration
remains
unclear.
This
study
demonstrates
that
is
downregulated
at
border
zone
cardiomyocytes
of
both
neonatal
apical
resection
myocardial
infarction.
Analysis
the
Single-cell
transcriptome
database
reveals
reduced
expression
population
with
high
capacity.
Cardiomyocyte-Foxp1
loss-of-function
significantly
promotes,
whereas
cardiomyocytes-Foxp1
gain-of-function
suppresses
proliferation.
Mechanistically,
directly
ubiquitin
specific
peptidase
20
(USP20),
de-ubiquitinase
prevents
hypoxia
inducible
factor
1ɑ
(HIF1α)
degradation.
Thus,
HIF1α
downstream
neural
crest
derivatives
expressed
1
(Hand1)
control
via
metabolic
transition
from
fatty
acid
oxidation
glycolysis.
Finally,
cardiac
type
troponin
T2
(cTnT)-promoter-driven
adeno-associated
virus
9
(AAV9)
for
Hand1
induction
promoted
functional
recovery.
These
findings
may
provide
novel
molecular
strategies
promote
therapeutic
interventions
failure.
Deleted Journal,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Feb. 27, 2025
Abstract
Tissue
regeneration
has
raised
intensive
attention
due
to
its
great
significance
in
overcoming
various
diseases
resulting
from
different
injuries.
Since
the
COVID‐19
pandemic,
mRNA
therapeutics
have
emerged
as
innovative
strategies
prevention
and
treatment
of
their
unique
advantages.
Compared
traditional
regenerative
strategies,
therapy
offers
rapid
translation
into
proteins
with
low
production
cost
high
modifiability.
Herein,
we
discuss
progress
key
processes
therapy,
focusing
on
therapeutic
modification
delivery
carriers.
The
preclinical
clinical
studies
for
cardiac,
lung,
liver,
kidney,
locomotor
system,
skin
lesions
neurological
disorders
were
summarized
comprehensively.
Developing
reduce
immunogenicity
off‐target
effects,
well
optimization
system
may
accelerate
pace
translation.
