Aterosclerosis

Solo disponible en BuenasTareas
  • Páginas : 29 (7096 palabras )
  • Descarga(s) : 0
  • Publicado : 19 de octubre de 2010
Leer documento completo
Vista previa del texto
insight review articles

Inflammation in atherosclerosis
Peter Libby
Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA (e-mail: plibby@rics.bwh.harvard.edu)

Abundant data link hypercholesterolaemia to atherogenesis. However, only recently have we appreciated that inflammatory mechanisms coupledyslipidaemia to atheroma formation. Leukocyte recruitment and expression of pro-inflammatory cytokines characterize early atherogenesis, and malfunction of inflammatory mediators mutes atheroma formation in mice. Moreover, inflammatory pathways promote thrombosis, a late and dreaded complication of atherosclerosis responsible for myocardial infarctions and most strokes. The new appreciation of the roleof inflammation in atherosclerosis provides a mechanistic framework for understanding the clinical benefits of lipid-lowering therapies. Identifying the triggers for inflammation and unravelling the details of inflammatory pathways may eventually furnish new therapeutic targets.

ardiovascular disease, currently the leading cause of death and illness in developed countries, will soon become thepre-eminent health problem worldwide1. Atherosclerosis — a progressive disease characterized by the accumulation of lipids and fibrous elements in the large arteries — constitutes the single most important contributor to this growing burden of cardiovascular disease. Our views of the pathophysiology of this important malady have evolved substantively over the past century. The link between lipidsand atherosclerosis dominated our thinking until the 1970s, based on strong experimental and clinical relationships between hypercholesterolaemia and atheroma2. The emerging knowledge of vascular biology led to a focus on growth factors and the proliferation of smooth muscle cells in the 1970s and 1980s. The daunting clinical problem of restenosis (narrowing of the vessel lumen) following arterialintervention, considered a problem of proliferation, reinforced this interest in vascular growth control. A fusion of these views led to the concept of the atheroma as a graveyard of acellular lipid debris enrobed by a capsule of proliferated smooth muscle cells. Over the past decade, however, we have come to appreciate a prominent role for inflammation in atherosclerosis and its complications.Whereas most clinicians previously regarded atheroma as a bland lesion, the current notion that inflammation and immune response contribute to atherogenesis has garnered increased interest3. As laboratory advances in vascular biology enabled new thinking about the clinical aspects of atherosclerosis, so too have emerging clinical data instructed our laboratory work, shifting its emphasisconsiderably. Formerly focused on luminal narrowing due to the bulk of atheroma, our current concepts recognize the biological attributes of the atheroma as key determinants of its clinical significance. This review will weave together laboratory and clinical advances to provide an update on inflammation in atherosclerosis.

C

Inflammation and the initiation of the atherosclerosis
The time-testedassociation of cholesterol with atherosclerosis stimulated a century-long study of the mechanisms linking lipids with atheroma. From the early years of the twentieth century onward, the pathogenesis of experimental atherosclerosis induced by hypercholesterolaemia has yielded to scrutiny at ever-deeper degrees of analysis. Indeed, instigation of inflammation may well link hyperlip868

idaemia toatherogenesis mechanistically. Soon after initiating an atherogenic diet, light microscopy reveals attachment of blood leukocytes to the endothelial cells that line the intima, the innermost layer of arteries4. Under ordinary circumstances, the endothelial monolayer in contact with flowing blood resists firm adhesion of leukocytes. We now possess considerable information about the molecular...
tracking img