bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 28, 2025
Biological
sex
plays
a
crucial
role
in
the
outcomes
of
cardiac
health
and
therapies.
Sex
hormones
are
known
to
strongly
influence
remodeling
through
intracellular
signaling
pathways,
yet
their
underlying
mechanisms
remain
unclear.
To
address
this
need,
we
developed
validated
logic-based
systems
biology
model
cardiomyocyte
hypertrophy
that,
for
first
time,
incorporates
effects
both
estradiol
(E2)
testosterone
(T)
alongside
well-established
hypertrophic
stimuli
(Strain,
angiotensin
II
(AngII),
endothelin-1
(ET-1)).
We
qualitatively
literature
data
with
84%
agreement.
Quantitative
validation
was
done
by
simulating
impact
inputs
(E2,
T,
Strain,
AngII,
ET-1)
on
hypertrophy,
captured
as
change
CellArea.
perturbed
examine
differential
response
identify
changes
influential
sensitive
downstream
nodes
male,
pre-menopausal
female,
post-menopausal
female
condition.
Our
results
suggest
that
T
has
greater
than
E2.
This
increases
our
understanding
which
can
aid
developing
more
effective
therapies
all
patients.
Differences
between
male
hearts
extend
far
beyond
size
structure.
play
key
roles
sex-specific
via
pathways.
Understanding
how
these
is
critical
effective,
approaches
cardiovascular
care.
Logic-based
models
have
proven
useful
quantifying
analyzing
complex
intricate
network
dynamics
various
cell
types.
leverage
method
develop
which,
includes
effect
testosterone.
Considering
combined
important
because
women
men
varying
concentrations
throughout
lives.
The
based
previously
published
studies.
then
investigated
differences
pre-
men.
Journal of Cardiovascular Translational Research,
Год журнала:
2023,
Номер
16(6), С. 1287 - 1302
Опубликована: Июль 21, 2023
Abstract
Cardiomyopathy
has
variable
penetrance.
We
analyzed
age
and
sex-related
genetic
differences
in
1,397
cardiomyopathy
patients
(Ontario,
UK)
with
whole
genome
sequencing.
Pediatric
cases
(n
=
471)
harbored
more
deleterious
protein-coding
variants
Tier
1
genes
compared
to
adults
926)
(34.6%
vs
25.9%
respectively,
p
0.0015),
variant
enrichment
constrained
coding
regions.
had
a
higher
burden
of
sarcomere
lower
channelopathy
gene
adults.
Specifically,
pediatric
MYH7
MYL3
hypertrophic
cardiomyopathy,
fewer
TTN
truncating
dilated
cardiomyopathy.
clustered
the
myosin
head
neck
domains
children.
OBSCN
was
top
mutated
adults,
enriched
for
protein-truncating
variants.
In
female
z-disc
males.
Genetic
may
explain
variability
Genotype-guided
predictions
onset
can
inform
pre-test
counseling.
Graphical
were
likely
be
genotype-positive
than
MYH7,
MYL3,
TNNT2,
VCL
.
Adults
Females
(DCM)
The Journal of Cardiovascular Aging,
Год журнала:
2022,
Номер
unknown
Опубликована: Янв. 1, 2022
Aging
promotes
structural
and
functional
remodeling
of
the
heart,
even
in
absence
external
factors.
There
is
growing
clinical
experimental
evidence
supporting
existence
sex-specific
patterns
cardiac
aging,
some
cases,
these
sex
differences
emerge
early
life.
Despite
efforts
to
identify
understanding
how
are
established
regulated
remains
limited.
In
addition
contributing
age-related
heart
disease,
also
appear
underlie
differential
responses
stress
such
as
adrenergic
activation.
Identifying
underlying
mechanisms
may
facilitate
characterization
disease
phenotypes,
with
ultimate
goal
utilizing
therapeutic
approaches
for
disease.
The
purpose
this
review
discuss
implications
changes
render
more
susceptible
we
can
target
age-
advance
therapies
both
male
female
patients.
AJP Heart and Circulatory Physiology,
Год журнала:
2022,
Номер
323(3), С. H538 - H558
Опубликована: Авг. 5, 2022
The
risks
of
heart
diseases
are
significantly
modulated
by
age
and
sex,
but
how
these
factors
influence
baseline
cardiac
gene
expression
remains
incompletely
understood.
Here,
we
used
RNA
sequencing
mass
spectrometry
to
compare
in
female
male
young
adult
(4
mo)
early
aging
(20
mouse
hearts,
identifying
thousands
age-
sex-dependent
signatures.
Sexually
dimorphic
genes
broadly
distributed,
functioning
mitochondrial
metabolism,
translation,
other
processes.
In
parallel,
found
over
800
with
differential
response
between
female,
including
cAMP
PKA
signaling.
Analysis
the
sex-adjusted
transcriptome
revealed
a
widespread
remodeling
exon
usage
patterns
that
is
largely
independent
from
expression,
concomitant
upstream
changes
RNA-binding
protein
splice
factor
transcripts.
To
evaluate
impact
splicing
events
on
proteoform
composition,
applied
an
RNA-guided
proteomics
computational
pipeline
analyze
data
detected
hundreds
putative
variant
proteins
have
potential
rewire
proteome.
Taken
together,
results
here
suggest
associated
1)
sex-biased
2)
rewiring
programs,
sex-
age-dependent
usages
structure
function.
These
contribute
emerging
evidence
for
considerable
sexual
dimorphism
process
should
be
considered
search
disease
mechanisms.NEW
&
NOTEWORTHY
Han
et
al.
proteogenomics
hearts
at
4
20
mo.
Sex-biased
function
autophagy,
Hundreds
show
sex-by-age
interactions,
is,
genes.
Cardiac
accompanied
functionally
coordinated
genes,
factors.
features
represent
underinvestigated
aspect
may
relevant
mechanisms.
Journal of Cardiovascular Development and Disease,
Год журнала:
2022,
Номер
9(3), С. 90 - 90
Опубликована: Март 19, 2022
Cardiovascular
diseases
(CVD)
are
the
leading
cause
of
morbidity
and
mortality.
Interestingly,
male
female
patients
with
CVD
exhibit
distinct
epidemiological
pathophysiological
characteristics,
implying
a
potentially
important
role
for
primary
secondary
sex
determination
factors
in
heart
development,
aging,
disease
therapeutic
responses.
Here,
we
provide
concise
review
field
discuss
current
gaps
knowledge
as
step
towards
elucidating
“sex
determination–heart
axis”.
We
specifically
focus
on
cardiovascular
manifestations
abnormal
humans,
such
Turner
Klinefelter
syndromes,
well
differences
cardiac
regenerative
potential
between
species
plastic
non-plastic
sexual
phenotypes.
Sex-biased
repair
mechanisms
also
discussed
steroid
hormone
17β-estradiol.
Understanding
axis”
may
offer
new
possibilities
enhanced
regeneration
and/or
post-injury.
AJP Heart and Circulatory Physiology,
Год журнала:
2023,
Номер
324(4), С. H542 - H552
Опубликована: Фев. 17, 2023
This
meta-analysis,
which
consisted
of
a
scoping
review
and
retrospective
medical
record
review,
is
focused
on
potential
sex
differences
in
cardiovascular
diseases
patients
with
Down
syndrome.
We
limited
our
to
peer-reviewed,
primary
articles
the
English
language,
PubMed
Web
Science
databases
from
1965
2021.
Guidelines
for
reviews
were
followed
throughout
process.
Four
categorical
domains
identified
searched
using
additional
keywords:
Circulation Research,
Год журнала:
2023,
Номер
133(1), С. 48 - 67
Опубликована: Май 31, 2023
Left
ventricular
noncompaction
(LVNC)
is
a
prevalent
cardiomyopathy
associated
with
excessive
trabeculation
and
thin
compact
myocardium.
Patients
LVNC
are
vulnerable
to
cardiac
dysfunction
at
high
risk
of
sudden
death.
Although
sporadic
inherited
mutations
in
genes
implicated
LVNC,
understanding
the
mechanisms
responsible
for
human
limited.
Acta Physiologica,
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 12, 2024
Abstract
A
unique
interplay
between
body
and
environment
embeds
reflects
host–microbiome
interactions
that
contribute
to
sex‐differential
disease
susceptibility,
symptomatology,
treatment
outcomes.
These
differences
derive
from
individual
biological
factors,
such
as
sex
hormone
action,
sex‐divergent
immune
processes,
X‐linked
gene
dosage
effects,
epigenetics,
well
their
interaction
across
the
lifespan.
The
gut
microbiome
is
increasingly
recognized
a
moderator
of
several
systems
are
thus
impacted
by
its
function
composition.
In
humans,
components
further
interact
with
gender‐specific
exposures
dietary
preferences,
stressors,
life
experiences
form
complex
whole,
requiring
innovative
methodologies
disentangle.
Here,
we
summarize
current
knowledge
among
hormones,
microbiota,
system,
vascular
health
relevance
for
epidemiology
cardiovascular
diseases.
We
outline
clinical
implications,
identify
gaps,
place
emphasis
on
required
future
studies
address
these
gaps.
addition,
provide
an
overview
caveats
associated
conducting
research
require
consideration
sex/gender
differences.
While
previous
work
has
inspected
separately,
here
call
attention
translational
utility
combined
perspective
research,
gender
medicine,
biology.
Physiological Reviews,
Год журнала:
2022,
Номер
103(1), С. 391 - 432
Опубликована: Авг. 12, 2022
The
heart
is
imbued
with
a
vast
lymphatic
network
that
responsible
for
fluid
homeostasis
and
immune
cell
trafficking.
Disturbances
in
the
forces
regulate
microvascular
movement
can
result
myocardial
edema,
which
has
profibrotic
proinflammatory
consequences
contributes
to
cardiovascular
dysfunction.
This
review
explores
complex
relationship
between
cardiac
lymphatics,
disease.
It
covers
revised
paradigm
of
around
capillary
as
well
arsenal
preclinical
tools
animal
models
used
model
edema
Clinical
studies
their
prognostic
significance
are
examined
parallel
recent
elegant
discerning
pathophysiological
role
therapeutic
potential
lymphatics
different
disease
models.
highlights
outstanding
questions
interest
both
basic
scientists
clinicians
regarding
roles
health
