الفهرس 
Title pageOnly 14 pages are availabe for public view
 |  | from | 66 |  |  |
| | | from | 66 | | |
Abstract
Atherosclerosis is a major risk factor for coronary and peripheral artery disease, accounts for the majority of deaths in North-America and western Europe and in developing countries.
Vascular endothelium is a versatile multifunctional tissue that has many synthetic and metabolic properties. As a semi-permeable membrane, endothelium controls the transfer of small and large molecules into the arterial wall and through walls of capillaries and vessels.
Moreover endothelial cells play a role in the maintenance of a non-thrombogenic blood-tissue interface, the modulation of blood flow and vascular resistance.
In addition to contributing to the formation of thrombi, endothelial injury may be responsible for the initiation of atherosclerosis and vascular lesions which are followed by monocyte infiltration, macrophage differentiation, and smooth muscle cell migration.
So damage to endothelium is an important component of atherosclerosis and can be qualified by measuring plasma markers such as von Willebrand factor (vWF) and E-selectin.
Intima-Media thickness (IMT) is a non invasive marker of early arterial wall alteration and is one method of assessing the development of early atherosclerosis.
Peroxisome proliferators activated receptors (PPARs) are ligand-activated transcription factors which function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. They include PPAR-alpha, PPAR-beta, PPAR gamma, and PPAR-delta.
PPAR-alpha is highly expressed in liver, muscle, kidney and heart, where it stimulates the beta-oxidative degradation of fatty acids. PPAR-gamma is predominantly expressed in intestine and adipose tissue, where it triggers adipocyte differentiation and promotes lipid storage.
The expression of PPAR-alpha and PPAR-gamma was reported in cells of vascular wall, such as monocyte, macrophages, endothelial and smooth muscle cells.
Furthermore, fatty acids-derivatives and eicosanoids are PPAR ligands. PPAR-alpha is activated by leukotriene B4, where as prostaglandin J2 is a PPAR-gamma ligand as well as some components oxidized LDL.
Leukotrienes take a parts in the regulation of the permeability of the capillaries in migration of leukocytes, the formation of inflammatory processes and in the evokation of asthma bronchiole.
LTB4 has been shown to be a potent chemoattactant for neutrophils both in vivo and in vitro. LTB4 has been found to stimulates monocyte migration in an agarose micro-DROPlet assay.
Oxidation of low-density lipoprotein (LDL) is a key process in atherogenesis and vitamin E (alpha – tocopherol, TOH) has received attention for its potential to attenuate the disease so antioxidant supplements prevent LDL oxidation and hence atherogenesis.
LDL must be seeded with reactive oxygen species before it can be oxidized. Albumin was capable of removing biologically active lipid from mildly oxidized LDL.
vWF is a large adhesive multimeric glycoprotein present in plasma, platelets and sub-endothelium. It is synthesized as a large precursor that consist of a signal peptide, a propeptide (von Willebrand antigen II) and von Willebrand subunit. It has two main functions of acting as a carrier and stabilizer of factor VIII and acts as a bridge in platelet adhesion to the exposed sub-endothelium of damaged vessels. Circulating vWF undergoes proteolytic cleavage under physiological conditions thus it can be distinguished from platelet vWF, which is not proteolyzed.
Vascular endothelium is the primary source of the synthesis and release of plasma vWF, the other type of cell that synthesized vWF is the megakaryocyte (Approximately 15% of the vWF is produced in megakaryocyte).
The present study was planned to find the following relationships between:
a- Levels of natural activators of (PPAR-alpha, PPAR-gamma) namely leukotriene B4 (LTB4) and oxidized low denisty lipoprotein (ox-LDL) respectively, and the marker of endothelial dysfunction von Willebrand factor (vWF).
b- The flow mediated dilation (FMD) response in brachial artery and intima-media thickness (IMT) in patients with peripheral and coronary artery disease.
In this study, we took thirty (30) patients aged from (55-65) years suffering from atherosclerosis. The results showed that vWF, LTB4 and ox-LDL are elevated in patients with peripheral and coronary artery disease. (i.e. There is a significant positive correlation between parameters).
The results showed that the parameters is much higher in patients than in control group.
Finally we conclude that:
1- Atherosclerosis is a generalized systemic disease that involves arterial structure and function.
2- Both biophysical {Flow Mediated Dilation (FMD) and Glyceryl Nitrate (GTN%)} and biochemical (vWF) aspects of vascular endothelium deteriorates in parallel with disease progression and can be used as diagnostic markers of atherosclerosis.
3- The standard accurate non-invasive methods to assess ankle-brachial index, compliance and distensibility proved to be the most predictive for the presence of extent of PAOD severity.
4- vWF, LTB4 and ox-LDL are elevated in patients with peripheral and coronary artery disease, so they can be used as marker of the disease.