A composite patch loaded with 2-Deoxy Glucose facilitates cardiac recovery after myocardial infarction via attenuating local inflammatory response
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Sept. 2, 2024
Local
inflammatory
microenvironment
in
the
early
stage
of
myocardial
infarction
(MI)
severely
impaired
cardiac
recovery
post-MI.
Macrophages
play
a
pivotal
role
this
process.
A
classical
glycolytic
inhibitor,
2-Deoxy-Glucose
(2-DG),
has
been
found
to
regulate
excessive
pro-inflammatory
macrophage
polarization
infarcted
myocardium.
This
study
investigated
effect
2-DG-loaded
chitosan/gelatin
composite
patch
on
infarct
post-MI
and
its
impact
repair.
The
results
showed
that
2-DG
significantly
inhibited
expression
cytokines,
alleviated
reactive
oxygen
species
(ROS)
accumulation,
repressed
proinflammatory
macrophages,
attenuated
local
ischemic
hearts,
as
well
improved
function,
reduced
scar
size,
promoted
angiogenesis
In
terms
mechanism,
exerts
anti-inflammatory
effects
through
inhibiting
NF-κB
signaling
pathway
reducing
assembly
activation
NLRP3
inflammasome.
These
findings
suggest
may
represent
promising
therapeutic
strategy
for
repair
after
MI.
Language: Английский
Angiotensin 1–7 Attenuates the Development of Ischemia–Reperfusion‐Induced Arrhythmia in Rats: Electrophysiology, Molecular, and Immunohistochemical Study
Microscopy Research and Technique,
Journal Year:
2025,
Volume and Issue:
unknown
Published: Jan. 27, 2025
ABSTRACT
Arrhythmia
is
a
common
and
serious
global
health
problem,
contributing
to
cardiovascular
morbidity
mortality.
The
cardiac
muscle
susceptible
ischemia–reperfusion
(I/R)
injury,
which
can
lead
fatal
arrhythmias
during
open‐heart
surgery.
We
investigated
the
potential
prophylactic
effect
of
angiotensin
1–7
(Ang
1–7)
using
an
in
vivo
rat
model
I/R
injury
examined
underlying
mechanisms.
Rats
were
treated
with
Ang
(1
mg/kg,
IP)
30
min
before
surgical
procedures.
Twenty‐four
rats
equally
divided
into
four
groups:
sham
control,
sham‐treated
1–7,
group,
group
1–7.
In
was
induced
by
clamping
left
coronary
artery
for
min,
followed
1
hour
reperfusion.
showed
abnormal
electrophysiological
changes
arrhythmic
episodes
electrocardiography
(ECG)
recording,
increased
oxidative
stress,
downregulation
peroxisome
proliferator‐activated
receptor
gamma
(PPAR‐γ),
upregulation
C‐X‐C
motif
chemokine
ligand
16
(CXCL16)
expression
tissue,
NF‐kB
IL‐17
levels.
Moreover,
caused
significant
histological
disruption
cyclooxygenase
2
(COX‐2)
heat
shock
protein
90
(HSP90)
immunoreactions,
correlating
extent
damage.
However,
preoperative
administration
significantly
improved
electrophysiological,
biochemical,
histopathological
injury.
This
study
demonstrated
that
exerted
protective
anti‐arrhythmic,
anti‐inflammatory,
pro‐healing
effects
upregulating
PPAR‐γ
downregulating
CXCL16,
IL‐17,
pathways,
suggesting
it
promising
cardioprotective
agent
preventing
Language: Английский
Alamandin and especially melatonin attenuate pulmonary arterial hypertension induced by monocrotalin
Fundamental and Clinical Pharmacology,
Journal Year:
2024,
Volume and Issue:
38(6), P. 1143 - 1154
Published: Aug. 11, 2024
Abstract
Background
Despite
the
available
treatments,
pulmonary
arterial
hypertension
(PAH)
prognosis
is
poor.
Objectives
We
aimed
to
investigate
effects
of
alamandine
(ALA),
melatonin
(MEL),
and
ALA
+
MEL
in
PAH.
Methods
The
rats
were
randomly
divided
into
Control
(
n
=
10),
monocrotaline
(MCT)
12),
12)
groups.
PAH
was
induced
by
MCT.
ALA,
MEL,
groups
received
50
μg/kg/day
10
mg/kg/day
respectively,
for
35
days.
Echocardiographic
hemodynamic
measurements
tissue
analyses
(morphometric,
histopathological,
ELISA,
western
blot)
performed.
Results
Monotherapies,
especially
reduced
right
ventricular
(RV)
systolic
pressure.
Only
increased
artery
acceleration
time.
MCT
RV/left
ventricle
(LV)
interventricular
septum
(IVS)
ratio.
While
slightly
decreased
RV/(LV
IVS),
significantly
restored
it.
tunica
intima‐media
(TIM)
thickness,
PCNA
α‐SMA
arterioles,
histopathological
score
(HS)
(inflammatory
infiltration
etc.)
lung,
RV.
All
treatments
TIM
thickness
(especially
MEL),
PCNA,
α‐SMA.
HS
lung;
however,
produced
greater
benefits.
attenuated
caused
a
significant
increase
lung
lysyl
oxidase
(LOX)
activity.
LOX;
provided
improvement.
Nrf‐2
MCT‐treated
rats,
Conclusion
attenuate
protect
RV
via
antiproliferative,
anti‐remodeling,
antihypertrophic,
anti‐inflammatory,
free
radical
scavenging
(only
MEL)
capabilities.
Overall,
best
outcomes.
Language: Английский
Comprehensive review on neprilysin (NEP) inhibitors: design, structure-activity relationships, and clinical applications
Frontiers in Pharmacology,
Journal Year:
2024,
Volume and Issue:
15
Published: Dec. 23, 2024
Neprilysin
(NEP),
a
zinc-dependent
membrane-bound
metallopeptidase,
regulates
various
bioactive
peptides,
particularly
in
kidneys,
vascular
endothelium,
and
the
central
nervous
system.
NEP’s
involvement
metabolizing
natriuretic
insulin,
enkephalins
makes
it
promising
target
for
treating
cardiovascular
Alzheimer’s
diseases.
Several
NEP
inhibitors,
such
as
sacubitril
omapatrilat,
have
been
approved
clinical
use,
which
inhibit
activity
to
prolong
bioactivity
of
beneficial
thereby
exerting
therapeutic
effects.
However,
despite
broad
application
prospects
they
still
specific
adverse
reactions
side
effects,
hypotension,
renal
impairment,
potentially
increased
risk
disease.
This
manuscript
comprehensively
reviews
progress
on
single-target
dual-target
inhibitors.
Dual-target
inhibitors
often
combine
with
other
targets,
angiotensin
receptors,
enhance
effects
reduce
reactions.
The
article
also
emphasizes
these
inhibitors'
design
strategies,
structure-activity
relationships
(SAR),
safety,
performance.
Language: Английский