الفهرس 
Aim of the workOnly 14 pages are availabe for public view
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Abstract
The development of MDS is a multiphasic process. Firstly, an
“initiating mutation”, or other genetic abnormality, is acquired in an
HSC, which primes the cell but is not sufficient to induce clinical
hematological disease. Subsequently, an additional mutation or
multiple mutations are acquired in either the HSC or downstream in the
myeloid progenitors, resulting in a proliferative advantage and an
impaired differentiation capacity.
While CHIP Clonal hematopoiesis of indeterminate potential
(CHIP) is characterized by the acquisition of somatic mutations in
HSCs which provide a competitive advantage over healthy HSCs,
leading to an increase in the number of mutated HSCs, progenitors and
their mature progeny.
Skeletal muscles modulate the inflammatory response mainly by
the secretion of myokines including irisin.The mechanisms involved in
irisin’s anti-inflammatory functions include reducing production of proinflammatory cytokines while increasing production of antiinflammatory cytokines, reducing macrophage proliferation, inducing
alternatively activated (M2-type) macrophage polarization, inhibiting
pathways of increased vascular permeability, and preventing the
formation of inflammasomes .
Atherogenesis is the process of forming plaques in the intima
layer of arteries. Atherosclerosis is developed progressively with
inflammation and lipid accumulation varying significantly among
Summary
64
individuals where Endothelial cells of the inner layer normally oppose
white blood cell attachment. Endothelial cells express adhesion
molecules, which in the initial stage of atherosclerosis capture
monocytes on their surfaces when influenced by irritative stimuli. The
adhesion of blood monocytes to the activated endothelial cells leads to
their migration into the intima.
Both the composition of the extracellular matrix beneath the
endothelium and the changes in endothelial permeability help also the
LDL particles that have cholesterol to migrate into the arterial wall .
Inside the intima, monocytes mature and transform into macrophages
that uptake the LDL particles to yield foam cells. Inside the growing
atheroma, the smooth muscle cells are transferred from the middle
layer of the arterial wall into the tunica intima . The smooth muscle
cells and macrophages die in advanced lesions by apoptosis. These
dead cells derive the extracellular lipid that builds up the plaque
composed of the lipid pool or the necrotic core.
This,study,aimed,to,measure,irisin,level,and,CIMT,and,to,unrave
l,their,correlations,with,other.variables. in.patients. with. MDS.
This case -control study was carried out on 80 subjects in the period
from November 2021 to March 2023 .Forty , sequentially selected MDS
patients from outpatient and inpatient of hematology divisions, internal
medicine departments of Menoufia and Zagazig university hospitals ,
Egypt and 40 sex and age matched healthy controls.All patients were ≥ 60
years old.Patients <60 years old, suspected secondary myelodysplasia ,
Summary
65
with known chronic liver disease, chronic kidney disease or chronic
inflammatory diseases were excluded.
All participants will be subjected to full history including
smoking , family history of premature coronary artery
disease,comprehensive clinical examination including blood pressure
and body mass index(BMI) calculation,laboratory investigations
including FBS, 2HPPS , HbA1c , lipid profile (total cholesterol,
triglycerides, HDL, and LDL) , homeostatic model assessment of
insulin resistance (HOMA-IR) ,high sensitivity CRP(HsCRP) and
homocysteine level,estimation of serum irisin level and Measurement
of CIMT .
Regarding cardiovascular risk factors , studied MDS patients had
significantly higher frequency of hypertension , median FBG , median
2hPPBG , median HbA1c , median HOMA-IR , median triglycerides ,
median HsCRP and median homocystiene than controls (P<0.05) ,
meanwhile the median HDL was significantly lower in patients
compared to controls (P<0.05); notworthy , there was no significant
difference between patients and controls regarding age , sex , smoking ,
BMI , family history of premature coronary artery disease , cholesterol
and LDL (P>0.05).Median irisin level was significantly lower in
patients than controls (P<0.05) , on the other hand , CIMT was
significantly higher in patients than controls (p<0.05).Irisin level was
significantly correlated with hemoglobin level , neutrophil count ,
platelet count and CIMT(P<0.05);where as CIMT was significantly
Summary
66
correlated with age , hemoglobin level , neutrophil count , platelet
count , HOMA-IR , 2hPPBG and irisin level (P <0.05)