| Atherosclerosis is a progressive disease characterized by the accumulation of lipids and fibrous elements in the arterial wall. Atherosclerosis is the underlying cause of myocardial infarction, infarctional stroke and coronary artery disease, which is the most common cause of death in Western societies and becomes an important killer of illness population. It is essential to treat and prevent the atherosclerosis and its complications in order to improve the health level and quality of life of our people. Elucidation of pathogenesis and etiology and involved mechanisms of atherosclerosis would surely therotically and practically shed light on the treatment and prevention of this disease.In the past half century, epidemiological study has revealed numerous risk factors for atherosclerosis. The traditional risk factors include hrpercholesterolemia, hypertension, cigrette smoking, obesity, diabetes mellitus, and so on. However, almost 50% patients suffered from atherosclerosis have none of these factors, indicating some other risk factors must be involved in. Identifying these unknown risk factors and their accompanying mechanisms will lead to novel therapeutic strategies, and mitigate the threatened effect from this disease. Nowadays, it is increasingly clear that inflammation play a pivotal role in pathogenesis of atherosclerosis. Injury of large and medium-sized artery and consequently inflammation have widespreadly been assumed to lead to atherosclerotic lesions.The attraction of leukocytes to tissues is essential for inflammation and the host response to infection. Recently, a group of small (8-14KD), structurally related cytokines- chemokines have been discovered and identified. Chemokines are a group of attractant cytokines, which induced directed migration of various types of leukocytes and so lead to inflammation by initiating and regulating the expression of adhesion molecule and directedly attracting inflammatory cells. At present, almost 50 members have been identified in human being. Chemokines can be subclassified by structure according to the number and spacing of conserved cysteines into four major groups, given the preferred names CXC (CXCL1-16), CC (CCL1-28), C (XCL1/2), and CX3C (CXCL1), which are used in the systematic nomenclatures. Based on themotif of Glu-Leu-Arg sequence, CXC chemokine can further be classified as CXC chemokine and non-ELR CXC chemokines. Generally, most ELR CXC chemokines are chemoattractants for neutrophils but not monocytes or lymphocytes; non-ELR CXC chemokines are chemoattractants for lymphocytes but not monocytes or neutrophils; CC chemokines attract monocytes and lymphocytes but not neutrophils. However, these distinctions are not without exceptions. Chemokines induce cell activation by binding to specific G-protein-coupled cell receptors (GPCR) on target cells.Immunohistochemical analysis of atherosclerotic lesions reveals a prominent leukocyte component. Of the leukocytes present in atheroma, approximately 80% are monocytes or monocytederived macrophages. Lymphocytes, on the other hand, constitute 5% to 20% of this cell population. The expression of a variety of chemokines is enhanced in inflammatory cells, endothelial cells and smooth muscle cells in atherosclerotic lesions. Peripheral blood mononuclear cells adhesion and migration to arterial endothelium is one of the earliest events in atherosclerosis. Enhanced expression of MCP-1 in atherosclerotic lesion has been showed and correlated with infiltration of monocytes. The important role of MCP-1 and its receptor CCR2 has been demonstrated in the animal model of atherosclerosis using gene knockout technology. Various other chemokines have been detected in atherosclerotic lesions and involved in the pathogenesis of atherosclerosis. |
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