Role of Inflammation in Atherosclerosis Associated with Rheumatoid Arthritis
Section snippets
Inflammatory mediators in rheumatoid arthritis and atherosclerosis
Although several factors contribute independently to the heightened cardiovascular risk observed in patients with RA, systemic inflammation likely contributes importantly. The cascade of events leading to atherosclerosis also participates in the pathogenesis of RA. Indeed, atherosclerosis and RA share a number of similarities, including T-cell and mast cell activation, production of proinflammatory cytokines such as tumor necrosis factor (TNF)–α and interleukin (IL)-6, and heightened expression
Endothelial dysfunction
Atherosclerotic plaques contain a variety of inflammatory and immune cells (mostly T cells and macrophages), smooth muscle cells, neovascular channels, an extracellular matrix rich in collagen and elastin, and a lipid-rich core underlying a usually intact but functionally abnormal endothelial lining in contact with the blood compartment.27, 32 Endothelial cell activation contributes early on to atherosclerosis development. Endothelial cells form the innermost surface of the artery wall and,
Plaque progression
Following the vascular wall infiltration of monocytes in early atherogenesis, monocytes develop into macrophages, and then into lipid-laden foam cells. Local expression of proinflammatory mediators such as M-CSF can amplify lesion formation and progression by promoting maturation, activation, and proliferation of mononuclear phagocytes in the intima.15, 47, 48ApoE-null mice deficient in M-CSF have considerably smaller atherosclerotic lesions and fewer advanced lesions than apoE−/− mice wild
Formation of an advanced lesion (fibrous plaque)
The evolution from fatty streak into a more complex lesion usually occurs over many years, a factor that underlies the potency of age as a risk factor for atherosclerotic events. The traditional view of this process involved evolution of fatty streaks into complicated lesions through multiplication and accumulation of smooth muscle cells in the plaque, producing an extensive extracellular matrix (Figure 2, Figure 3).27 According to current thinking, many coronary arterial lesions develop
Thrombotic complications of atheroma
Inflammation promotes not only the initiation and progression of the atherosclerotic lesion, but also the development of the complicated or disrupted lesion. As previously discussed, the concept of continuous growth of the atheroma has evolved into one of apparent bursts in atheroma growth, followed by physical disruption of the plaque (weakening of the fibrous cap that renders the plaque prone to rupture), which triggers thrombosis. Healing of disrupted plaques may lead to episodes of rapid
Summary
A large body of evidence supports the involvement of proinflammatory cytokines in the development and progression of atherosclerosis, processes that overlap considerably with the pathogenic processes seen in RA. Now considered an inflammatory disease, atherosclerosis involves the production of proinflammatory cytokines by immune cells, such as monocytes, macrophages, and T cells, at sites of atherosclerotic lesions as well as by intrinsic vascular, endothelial, and smooth muscle cells.15, 82
Author disclosures
The author of this article has disclosed the following industry relationships:
Peter Libby, MD, served on the Scientific Advisory Board of Interleukin Genetics.
Acknowledgment
I thank Rick Davis, MS, RPh, and Ms. Joan Perry for editorial assistance.
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