الفهرس | Only 14 pages are availabe for public view |
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) |