Eicosanoid Pathways and Inflammation in Sickle Cell Vaso-Occlusion: A Review
International Journal of Medical Sciences and Pharma Research,
Год журнала:
2024,
Номер
10(2), С. 47 - 53
Опубликована: Июль 15, 2024
Sickle
cell
anemia
(SCA)
is
a
genetic
blood
disorder
characterized
by
the
production
of
abnormal
hemoglobin
S,
leading
to
deformation
red
cells
(RBCs)
into
sickle
shape.
This
results
in
recurrent
vaso-occlusive
crises
(VOCs),
hallmark
disease,
which
are
driven
complex
interactions
between
sickled
RBCs,
inflammation,
and
endothelial
dysfunction.
Eicosanoids,
bioactive
lipid
mediators
derived
from
arachidonic
acid,
play
critical
role
inflammatory
response
associated
with
VOCs.
review
explores
various
eicosanoid
pathways
involved
SCA,
focusing
on
roles
prostaglandins,
leukotrienes,
lipoxins
modulating
inflammation
vascular
function.
The
dysregulation
synthesis
metabolism
significantly
contributes
pathophysiology
VOCs
SCA.
Elevated
levels
pro-inflammatory
prostaglandins
leukotrienes
exacerbate
increase
permeability,
promote
leukocyte
adhesion,
microvascular
obstruction
tissue
ischemia.
Conversely,
anti-inflammatory
may
be
impaired,
further
perpetuating
response.
Therapeutic
strategies
targeting
offer
promising
avenues
for
improving
clinical
outcomes
patients
Interventions
such
as
non-steroidal
drugs
(NSAIDs),
leukotriene
receptor
antagonists,
lipoxin
analogues
help
mitigate
prevent
Keywords:
anemia,
crisis,
eicosanoids,
COX
enzymes,
LOX
therapeutic
Язык: Английский
Glycocalyx Degradation and Endothelial Dysfunction in Vaso-Occlusion: A Review
International Journal of Medical Sciences and Pharma Research,
Год журнала:
2024,
Номер
10(2), С. 41 - 46
Опубликована: Июль 15, 2024
The
endothelial
glycocalyx
is
a
crucial
component
of
vascular
homeostasis,
acting
as
protective
barrier
and
regulator
function.
In
sickle
cell
anemia
(SCA),
the
degradation
significantly
contributes
to
dysfunction
pathogenesis
vaso-occlusive
crises
(VOCs).
This
review
examines
mechanisms
degradation,
including
roles
shear
stress,
enzymatic
activity,
oxidative
stress.
breakdown
leads
increased
permeability,
enhanced
adhesion,
impaired
nitric
oxide
(NO)
production,
all
which
exacerbate
promote
VOCs.
Mechanistically,
stress
mechanical
forces
from
altered
hemodynamics
in
SCA
disrupt
glycocalyx.
Enzymes
like
heparanase,
hyaluronidase,
matrix
metalloproteinases
degrade
components,
while
chronic
inflammation
hemolysis
further
accelerates
this
process.
resulting
manifests
promoting
reduced
NO
synthesis,
leading
vasoconstriction
thrombosis.
pro-thrombotic
environment
facilitates
adhesion
aggregation
sickled
red
blood
cells
(RBCs)
other
circulating
cells,
driving
Therapeutic
strategies
targeting
preservation
restoration
are
critical
for
mitigating
SCA.
Approaches
include
use
precursors,
synthetic
mimetics,
antioxidant
therapy,
enzyme
inhibitors,
donors.
These
therapies
aim
restore
glycocalyx,
reduce
improve
bioavailability,
thereby
reducing
incidence
severity
Continued
research
into
these
therapeutic
interventions
essential
optimizing
treatment
improving
clinical
outcomes
patients
with
Keywords:
Glycocalyx,
Endothelial
Dysfunction,
Vaso-Occlusion,
Sickle
Cell
Anemia,
Inflammation,
Shear
Stress,
Cells
Язык: Английский
Influence of Hemoglobin Variants on Vaso-Occlusive Phenomena in Sickle Cell Anemia: A Review
International Journal of Medical Sciences and Pharma Research,
Год журнала:
2024,
Номер
10(2), С. 54 - 59
Опубликована: Июль 15, 2024
Sickle
cell
anemia
(SCA)
is
a
genetic
disorder
characterized
by
the
presence
of
abnormal
hemoglobin
S
(HbS),
leading
to
sickling
red
blood
cells
(RBCs)
and
subsequent
vaso-occlusive
crises
(VOCs).
These
are
responsible
for
acute
pain
episodes
potential
organ
damage,
significantly
affecting
quality
life
individuals
with
SCA.
The
clinical
presentation
SCA
can
be
modified
various
variants,
including
C
(HbC)
E
(HbE),
which
influence
severity
frequency
VOCs
through
alterations
in
morphology,
oxygen
affinity,
inflammatory
responses.
variants
affect
rigidity
aggregation,
enhanced
vascular
occlusion
increased
susceptibility
VOCs.
Hemoglobin
C,
instance,
results
more
rigid
RBCs
that
readily
adhere
endothelium,
while
may
reduce
degree
due
its
higher
affinity.
Furthermore,
these
modulate
response,
influencing
recruitment
leukocytes
activation
endothelial
cells,
thereby
contributing
overall
pathophysiology
Individualized
treatment
approaches,
such
as
hydroxyurea
therapy
emerging
gene
therapies,
tailored
based
on
specific
variant
present
patient.
Continued
research
crucial
elucidate
complex
interactions
between
VOCs,
ultimately
improved
patient
outcomes
those
affected
sickle
anemia.
Keywords:
anemia,
crises,
S,
E,
occlusion,
inflammation,
therapeutic
strategies
Язык: Английский
Nitric Oxide Dysregulation and Vaso-Occlusive Crisis in Sickle Cell Anemia: A Review
International Journal of Medical Sciences and Pharma Research,
Год журнала:
2024,
Номер
10(2), С. 36 - 40
Опубликована: Июль 15, 2024
Sickle
cell
anemia
(SCA)
is
a
genetic
disorder
characterized
by
the
production
of
abnormal
hemoglobin
S
(HbS),
leading
to
chronic
hemolysis
and
recurrent
vaso-occlusive
crises
(VOCs).
VOCs
are
acute,
painful
episodes
caused
obstruction
blood
flow
due
sickled
red
cells
(RBCs),
resulting
in
tissue
ischemia
organ
damage.
Nitric
oxide
(NO)
plays
crucial
role
vascular
homeostasis,
its
dysregulation
significant
factor
pathophysiology
SCA,
particularly
VOCs.
In
releases
free
into
plasma,
which
scavenges
NO
reduces
bioavailability.
Additionally,
increased
arginase
activity
depletes
L-arginine,
substrate
for
synthesis,
further
diminishing
production.
Oxidative
stress
exacerbates
degradation
endothelial
dysfunction,
amplifying
risk
The
interplay
between
deficiency,
oxidative
stress,
dysfunction
creates
vicious
cycle
that
perpetuates
damage
increases
frequency
severity
This
review
explores
mechanisms
underlying
SCA
impact
on
function.
It
also
discusses
potential
therapeutic
interventions
aimed
at
modulating
pathways
prevent
or
reduce
These
include
donors,
L-arginine
supplementation,
phosphodiesterase
inhibitors,
antioxidant
therapy,
inhibitors.
Keywords:
anemia,
crisis,
nitric
dysregulation,
hemolysis,
interventions.
Язык: Английский
Endoplasmic Reticulum Stress and Vaso-Occlusive Crisis in Sickle Cell Anemia: A Review
International Journal of Medical Sciences and Pharma Research,
Год журнала:
2024,
Номер
10(2), С. 60 - 64
Опубликована: Июль 15, 2024
ickle
cell
anemia
(SCA)
is
a
genetic
disorder
characterized
by
the
production
of
abnormal
hemoglobin,
specifically
hemoglobin
S
(HbS),
which
leads
to
sickling
red
blood
cells
(RBCs)
and
subsequent
microvascular
occlusion.
Vaso-occlusive
crises
(VOCs)
are
hallmark
SCA,
resulting
in
acute
pain
potential
organ
damage.
Recent
studies
have
highlighted
role
endoplasmic
reticulum
(ER)
stress
pathophysiology
as
it
contributes
accumulation
misfolded
proteins
activates
unfolded
protein
response
(UPR).
This
response,
while
initially
adaptive,
can
become
detrimental
when
prolonged,
leading
cellular
dysfunction
exacerbating
process.
The
relationship
between
ER
VOCs
involves
several
interconnected
mechanisms,
including
activation
pro-inflammatory
cytokines,
apoptosis
erythroid
precursor
cells,
oxidative
stress.
stress-induced
inflammation
promotes
adhesion
sickled
RBCs
leukocytes
endothelium,
enhancing
obstruction.
Additionally,
effects
on
erythropoiesis
lead
further
hypoxia,
creating
vicious
cycle
that
perpetuates
risk
VOCs.
Understanding
these
mechanisms
provides
critical
insights
into
complexities
SCA
factors
contribute
frequency
severity
Targeting
pathways
presents
novel
therapeutic
strategy
improve
clinical
outcomes
patients
with
SCA.
Pharmacological
agents
alleviate
or
modulate
UPR
may
enhance
RBC
function
reduce
incidence
Keywords:
Sickle
anemia,
vaso-occlusive
crisis,
stress,
inflammation,
strategies
Язык: Английский