doi: 10.1161/01.ATV.0000149672.83911.5b
© 2004 American Heart Association, Inc.
Editorials |
Glimpse of the Secret Life of the Plaque
From the Department of Medicine and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
Correspondence to Goran K. Hansson, Department of Medicine and Center for Molecular Medicine L8:03, Karolinska University Hospital, SE-17176 Stockholm, Sweden. E-mail Goran.Hansson@cmm.ki.se
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
For many years, atherosclerosis was thought to be a slow process of continuous growth of lesions. It was generally believed to be irreversible and to cause clinical symptoms when the sheer size of the plaque obstructed blood flow. This view has been completely changed during the last decade. Early studies of primates showed that whereas a high-cholesterol diet induced atherosclerotic lesions, a switch to low-fat diet led to regression of plaques within a few months.1 These findings revealed that the atherosclerotic process is much more dynamic than had previously been anticipated. When modern lipid-lowering drugs became available, patients with coronary heart disease were treated aggressively and their coronary circulation examined by repeated angiographies.2 Again, some plaques were found to regress on treatment. However, clinical studies showed more remarkable effects on clinical events than on the degree of stenosis,2 suggesting that regression therapy acts to modify the composition of the plaque as well as reducing its size.
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Analysis in experimental models have confirmed and extended these conclusions. When hypercholesterolemic rabbits were switched to a lipid-lowering diet, the composition of the lesions changed rapidly into a more stable phenotype.3,4 Smooth muscle cells accumulated and collagen increased whereas inflammation waned and signs of proteolytic and prothrombotic activity were reduced. All of these phenomena reflect the cellular dynamics of the atherosclerotic plaque, where metabolic changes impact on cell accumulation, differentiation, and gene expression. Whereas hyperlipidemic conditions promote the formation of large, vulnerable plaques with activated immune cells, intense inflammation, proteolysis, and
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Arterioscler Thromb Vasc Biol 2004 24: 2307-2312.