Role of Inflammation in Atherosclerosis

8527 words 35 pages
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
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Interleukin-8 (IL-8) may also have a similar
role as a leukocyte chemo-attractant during atherogenesis (Boisvert et al, 1998). A
family of T-cell chemo-attractants may also promote migration of lymphocytes into
the intima; atheroma overexpress other chemokines that may contribute to
lymphocyte recruitment, including a trio of CXC chemokines induced by interferon-
(IFN-) (Mach et al, 1999), which in turn causes the T-cells to elaborate inflammatory
cytokines such as IFN- and lymphotoxin (Tumour necrosis Factor (TNF), that are
capable of stimulating macrophages, vascular endothelial cells and also intimal
smooth muscle cells, leading to inflammation (Paoletti et al, 2004). Chemo-attraction
of mast cells found in atheroma probably depends on a CC chemokine; eotaxin, that is
usually over-expressed in these lesions (Haley et al, 2000). Once resident in the
arterial intima, monocytes acquire the morphological characteristics of macrophages.
A cytokine or growth factor produced in the inflamed intima; macrophage colonystimulating
factor (M-CSF), induces monocytes entering the plaque to differentiate
into macrophages. This step is critical for the development of atherosclerosis (Smith
et al, 1995), and is associated with up-regulation of pattern recognition receptors for
innate immunity, including scavenger receptors and toll-like receptors, which bind
and internalise a broad range of molecules and particles bearing

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