Role of Inflammation in Atherosclerosis

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disease, currently the leading cause of death and illness in the United States, Europe and most developed countries, is fast growing to become the preeminent health problem worldwide (Murray & Lopez, 1997). Atherosclerosis is a progressive disease of the large and intermediate-sized arteries characterized by accumulation of lipids and fibrous elements which cause development of fatty lesions called atheromatous plaques on the inside surfaces of the arterial walls; and is the single most important contributor to this growing burden of cardiovascular disease. Studies on the pathophysiology of this disease has evolved over the past three decades, and a fusion of these views has led to the concept of the atheroma as a graveyard of acellular lipid debris enrobed by a capsule of proliferated smooth muscle cells. Atherosclerosis, formerly considered as a bland lipid storage disease, actually involves an ongoing inflammatory response that results in a host of complications including ischaemia, acute coronary syndromes and stroke. Recent advances in cellular science have established a fundamental role for inflammation in mediating all stages of this disease, from initiation through progression, and ultimately, the thrombotic complications of atherosclerosis. These findings are providing important links between predisposing risk factors, and the mechanism of atherogenesis. The chronic inflammatory process involving the arterial endothelium, that ultimately results in the complications of atherosclerosis, may be caused by a response to the oxidative components of modified low-density lipoproteins (LDLderived from cholesterol), chronic infection (eg; Chlamydia pneumoniae), free radical generation, or other factors. Clinical markers of this process such as C-reactive protein (CRP) are becoming useful in predicting increased risk of coronary heart disease. The new appreciation of the role of inflammation in atherosclerosis has further elucidated the understanding of this disease, and is providing practical clinical applications in risk assessment, and targeting of therapy for this growing scourge of worldwide importance.

INFLAMMATORY MECHANISMS INVOLVED IN ATHEROSCLEROSISAtherosclerosis is a multifactorial, multistep disease that involves chronic inflammation at every stage, from initiation to progression, and eventually plaque rupture. In atherosclerosis, the normal homeostatic function of the endothelium are altered, and this promotes an inflammatory response mediated by monocytes, Tlymphocytes, macrophages, endothelial cells and smooth muscle cells (Prescott et al, 2002).

Recruitment of Inflammatory cells to the Arterial wall: The Initiation Phase Atherosclerotic plaque development begins with activation of the arterial endothelial cells, in response to oxidized low-density-lipoprotein cholesterol, injury, or infection. The infiltration and retention of LDL in the arterial intima initiate an inflammatory response in the artery wall. (Skalen et al, 2002). Oxidation or enzymatic modification of LDL in the intima, leads to the release of bioactive phospholipids that can activate endothelial cells (Hansson et al, 2006), and it is believed that this activation occurs preferentially at sites of haemodynamic strain (Nakashima et al, 1998). The platelet is the first blood cell to arrive at the scene of endothelial activation (Massberg et al, 2002). Its glycoproteins Ib and IIb/IIIa engage surface molecules on the endothelial cell, which may contribute to endothelial activation. Studies on hypercholesterolaemic mice showed that inhibition of platelet adhesion reduces leukocyte infiltration and atherosclerosis (Massberg et al, 2002). Activated endothelial cells over-express several types of leukocyte adhesion molecules, which cause blood cells rolling along the vascular surface to adhere at the site of activation (Eriksson et al, 2001). Since the normal healthy endothelium does not generally support leukocyte...
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