Single-cell and spatial analysis reveals the interaction between ITLN1+ foam cells and SPP1+ macrophages in atherosclerosis
Frontiers in Cardiovascular Medicine,
Journal Year:
2025,
Volume and Issue:
12
Published: Feb. 13, 2025
Introduction
Cardiovascular
disease
(CVD)
caused
by
atherosclerosis
(AS)
remains
the
leading
cause
of
mortality
in
developed
countries.
Understanding
cellular
heterogeneity
within
inflammatory
microenvironment
is
crucial
for
advancing
management
strategies.
This
study
investigates
regulatory
functions
distinct
cell
populations
AS
pathogenesis,
focusing
on
interaction
between
vascular
smooth
muscle
(VSMC)-derived
ITLN1
+
foam
cells
and
SPP1
FABP5
macrophages.
Methods
We
employed
single-cell
RNA
sequencing
to
characterize
plaques.
Correlation
analyses
CellChat
package
were
utilized
elucidate
intercellular
communication
networks
among
various
types.
The
functional
roles
key
subsets
macrophages
VSMCs
assessed
using
Gene
Ontology
(GO)
Kyoto
Encyclopedia
Genes
Genomes
(KEGG)
pathway
analyses.
Pseudotime
trajectory
analysis
was
conducted
explore
dynamics
VSMC
differentiation.
Additionally,
spatial
transcriptomics
used
demonstrate
physical
interactions
different
subpopulations.
Results
identified
significant
infiltration
macrophage
clusters
AS,
with
being
highly
enriched
These
associated
lipid
transport,
storage,
migration
pathways.
A
subset
derived
from
exhibited
robust
expression
markers
metabolism-related
genes.
indicated
that
represent
a
terminal
stage
differentiation,
characterized
elevated
genes
linked
synthesis
progression.
Spatial
revealed
macrophages,
mediated
MIF-(CD74
CD44)
SPP1-CD44
ligand-receptor
axes.
Discussion
Our
findings
underscore
critical
crosstalk
promoting
accumulation
Targeting
this
cell-cell
may
offer
new
therapeutic
avenues
managing
atherosclerosis.
Further
validation
these
mechanisms
necessary
develop
effective
immunotherapeutic
strategies
against
AS.
Language: Английский
Dual-Responsive Methotrexate-Human Serum Albumin Complex-Encapsulated Liposomes for Targeted and Enhanced Atherosclerosis Therapy
International Journal of Nanomedicine,
Journal Year:
2025,
Volume and Issue:
Volume 20, P. 2305 - 2322
Published: Feb. 1, 2025
In
plaque
sites
of
atherosclerosis
(AS),
the
physiological
barrier
caused
by
thick
fiber
cap
due
to
overmigration
vascular
smooth
muscle
cells
(VSMCs)
prevents
efficient
drug
delivery
damaged
macrophages.
How
ensure
precise
targeted
drugs
and
their
on-demand
release
dysfunctional
under
fibrous
are
feasible
solutions
enhance
AS
treatment.
A
small
complex
methotrexate
(MTX)-human
serum
albumin
(HSA)
with
strong,
penetration
ability
was
encapsulated
in
a
cholesterol
hemisuccinate
(CHEM)
prepared
pH-sensitive
liposome,
modifying
ROS-responsive
PEG2000-TK-DSPE
(PTD),
termed
PTD/Lipo/MTX-HSA.
PTD/Lipo/MTX-HSA
can
achieve
targeting
response
plaques
environments
AS.
The
designed
formulation
accelerated
small-sized
MTX-HSA
excess
ROS
acidic
pH
conditions,
it
better
penetrated
macrophage
spheroids.
Furthermore,
has
mouse
model
produce
good
anti-inflammatory
efficacy
inhibiting
p65
entry
into
nucleus
turn
out
inflammatory
factor.
Our
formulations
work
safety
mind,
also
highlights
potential
precisely
on-demand-released
dual-responsive
smart
nanoplatforms
as
promising
therapeutic
options
penetrate
deeper
for
effective
treatment
Language: Английский