Basic Research in Cardiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 8, 2024
Despite
accumulating
data
on
underlying
mechanisms,
the
influence
of
sex
and
prevalent
cardio-metabolic
co-morbidities
manifestation
severity
immune
checkpoint
inhibitor
(ICI)-induced
cardiotoxicity
has
not
been
well
defined.
To
elucidate
whether
affect
ICI-induced
cardiotoxicity,
we
randomized
17-month-old
male
female
mice
to
receive
control
diet
(CON)
or
high-fat
(HFD)
+
L-NAME-a
well-established
mouse
model
co-morbidities-for
17
weeks
(n
=
5-7),
evaluated
markers
T-cell
function
in
spleen.
As
expected,
HFD
L-NAME
significantly
increased
body-
heart
weight,
serum
cholesterol
levels,
caused
no
systolic
dysfunction,
however,
led
diastolic
cardiomyocyte
hypertrophy,
fibrosis
only
males
compared
corresponding
CON.
Western
blot
analyses
splenic
protein
levels
showed
differential
expression
depending
co-morbidities,
suggesting
exhaustion
both
sexes
L-NAME,
but
more
pronounced
males.
In
a
sub-study
with
similar
setup,
tested
cardiotoxic
manifestations
ICI
by
treating
anti-PD-1
monoclonal
antibody
(ICI)
for
last
2
administration
5-7).
After
treatment,
cardiac
functions
decreased
CON,
groups
baseline
(before
administration).
conclusion,
this
exploratory
study
using
aged
mice,
describe
first
time
that
ICI-related
dysfunction
is
diminished
when
obesity
hypercholesterolemia
are
present,
possibly
due
obesity-related
exhaustion.
Journal of Cardiovascular Development and Disease,
Год журнала:
2023,
Номер
10(8), С. 352 - 352
Опубликована: Авг. 18, 2023
Autophagy,
a
dynamic
and
complex
process
responsible
for
the
clearance
of
damaged
cellular
components,
plays
crucial
role
in
maintaining
myocardial
homeostasis.
In
context
heart
failure,
autophagy
has
been
recognized
as
response
mechanism
aimed
at
counteracting
pathogenic
processes
promoting
health.
Its
relevance
underscored
not
only
various
animal
models,
but
also
human
heart.
Extensive
research
efforts
have
dedicated
to
understanding
significance
unravelling
its
molecular
mechanisms.
This
review
aims
consolidate
current
knowledge
involvement
during
progression
failure.
Specifically,
we
provide
comprehensive
overview
published
data
on
impact
deregulation
achieved
by
genetic
modifications
or
pharmacological
interventions
ischemic
non-ischemic
models
Furthermore,
delve
into
intricate
mechanisms
through
which
regulates
within
three
predominant
cell
populations
heart:
cardiomyocytes,
cardiac
fibroblasts,
endothelial
cells.
Finally,
emphasize
need
future
unravel
therapeutic
potential
associated
with
targeting
management
Basic Research in Cardiology,
Год журнала:
2024,
Номер
119(5), С. 869 - 887
Опубликована: Май 25, 2024
Multiple
common
cardiovascular
comorbidities
produce
coronary
microvascular
dysfunction.
We
previously
observed
in
swine
that
a
combination
of
diabetes
mellitus
(DM),
high
fat
diet
(HFD)
and
chronic
kidney
disease
(CKD)
induced
systemic
inflammation,
increased
oxidative
stress
produced
endothelial
dysfunction,
altering
control
tone
via
loss
NO
bioavailability,
which
was
associated
with
an
increase
circulating
endothelin
(ET).
In
the
present
study,
we
tested
hypotheses
(1)
ROS
scavenging
(2)
ET
Basic Research in Cardiology,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 8, 2024
Despite
accumulating
data
on
underlying
mechanisms,
the
influence
of
sex
and
prevalent
cardio-metabolic
co-morbidities
manifestation
severity
immune
checkpoint
inhibitor
(ICI)-induced
cardiotoxicity
has
not
been
well
defined.
To
elucidate
whether
affect
ICI-induced
cardiotoxicity,
we
randomized
17-month-old
male
female
mice
to
receive
control
diet
(CON)
or
high-fat
(HFD)
+
L-NAME-a
well-established
mouse
model
co-morbidities-for
17
weeks
(n
=
5-7),
evaluated
markers
T-cell
function
in
spleen.
As
expected,
HFD
L-NAME
significantly
increased
body-
heart
weight,
serum
cholesterol
levels,
caused
no
systolic
dysfunction,
however,
led
diastolic
cardiomyocyte
hypertrophy,
fibrosis
only
males
compared
corresponding
CON.
Western
blot
analyses
splenic
protein
levels
showed
differential
expression
depending
co-morbidities,
suggesting
exhaustion
both
sexes
L-NAME,
but
more
pronounced
males.
In
a
sub-study
with
similar
setup,
tested
cardiotoxic
manifestations
ICI
by
treating
anti-PD-1
monoclonal
antibody
(ICI)
for
last
2
administration
5-7).
After
treatment,
cardiac
functions
decreased
CON,
groups
baseline
(before
administration).
conclusion,
this
exploratory
study
using
aged
mice,
describe
first
time
that
ICI-related
dysfunction
is
diminished
when
obesity
hypercholesterolemia
are
present,
possibly
due
obesity-related
exhaustion.
