Role of Inflammation in Atherosclerosis
INTRODUCTION
Cardiovascular
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
Cardiovascular
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
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