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The

new england journal

of

medicine

review article

mechanisms of disease

Inflammation, Atherosclerosis, and Coronary Artery Disease
Göran K. Hansson, M.D., Ph.D.

r

ecent research has shown that inflammation plays a key role in coronary artery disease (CAD) and other manifestations of atherosclerosis. Immune cells dominate early atherosclerotic lesions, their effectormolecules accelerate progression of the lesions, and activation of inflammation can elicit acute coronary syndromes. This review highlights the role of inflammation in the pathogenesis of atherosclerotic CAD. It will recount the evidence that atherosclerosis, the main cause of CAD, is an inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate, propagate, andactivate lesions in the arterial tree. A decade ago, the treatment of hypercholesterolemia and hypertension was expected to eliminate CAD by the end of the 20th century. Lately, however, that optimistic prediction has needed revision. Cardiovascular diseases are expected to be the main cause of death globally within the next 15 years owing to a rapidly increasing prevalence in developing countriesand eastern Europe and the rising incidence of obesity and diabetes in the Western world.1 Cardiovascular diseases cause 38 percent of all deaths in North America and are the most common cause of death in European men under 65 years of age and the second most common cause in women. These facts force us to revisit cardiovascular disease and consider new strategies for prediction, prevention, andtreatment.

From the Karolinska Institute, Center for Molecular Medicine, Department of Medicine, Karolinska University Hospital, Stockholm. Address reprint requests to Dr. Hansson at the Center for Molecular Medicine, L8:03, Karolinska University Hospital, SE17176 Stockholm, Sweden, or at goran. hansson@cmm.ki.se. N Engl J Med 2005;352:1685-95.
Copyright © 2005 Massachusetts Medical Society.main features of atherosclerotic lesions
Atherosclerotic lesions (atheromata) are asymmetric focal thickenings of the innermost layer of the artery, the intima (Fig. 1). They consist of cells, connective-tissue elements, lipids, and debris.2 Blood-borne inflammatory and immune cells constitute an important part of an atheroma, the remainder being vascular endothelial and smooth-muscle cells. Theatheroma is preceded by a fatty streak, an accumulation of lipid-laden cells beneath the endothelium.3 Most of these cells in the fatty streak are macrophages, together with some T cells. Fatty streaks are prevalent in young people, never cause symptoms, and may progress to atheromata or eventually disappear. In the center of an atheroma, foam cells and extracellular lipid droplets form a coreregion, which is surrounded by a cap of smooth-muscle cells and a collagen-rich matrix. T cells, macrophages, and mast cells infiltrate the lesion and are particularly abundant in the shoulder region where the atheroma grows.2,4,5 Many of the immune cells exhibit signs of activation and produce inflammatory cytokines.5-8 Myocardial infarction occurs when the atheromatous process prevents blood flowthrough the coronary artery. It was previously thought that progressive luminal narrowing from continued growth of smooth-muscle cells in the plaque was the main cause of infarction. Angiographic studies have, however, identified culprit lesions that do not cause marked stenosis,9 and it is now evident that the activation of plaque rather

n engl j med 352;16

www.nejm.org

april 21, 20051685

The

new england journal

of

medicine

A

C

Thrombus * Ruptured Lipid-rich core cap

Thrombus Smoothmuscle cell

Endothelium

B

*

Proteases, prothrombotic factors T cell

Mast cell Macrophage

Microbes, autoantigens, inflammatory molecules

Figure 1. Atherosclerotic Lesion in a Human Artery. Panel A shows a cross-sectioned coronary artery from a patient...
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