doi: 10.1161/CIRCRESAHA.107.162487
© 2007 American Heart Association, Inc.
Editorials |
Inflammation and Atherosclerosis
From Molekulare Innere Medizin, Departement für Innere Medizin, Universitätsspital Zürich, Switzerland.
Correspondence to Matthias Barton, MD, Medizinische Poliklinik, Departement für Innere Medizin, Universitätsspital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail barton@usz.ch
See related article, pages 792–801
Key Words: oxidized phospholipids • inflammation • vascular smooth muscle cells • differentiation marker genes • atherosclerosis
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The deleterious effects of high low-density lipoprotein (LDL) cholesterol levels on atherosclerosis has been known for almost a century,1 yet plasma cholesterol continues to be a challenge for clinicians in the treatment and prevention of cardiovascular disease.2,3 Atherogenesis involves uptake of cholesterol in the vascular wall, followed by inflammatory activation and growth of vascular smooth muscle cells.4,5 Indeed, proinflammatory mediators such as interleukins and cytokines stimulate vascular cell growth and atherogenesis (reviewed in4), whereas inhibition of inflammatory pathways attenuates cell growth and atherosclerosis.6 Therefore, we now view atherosclerosis as a vascular inflammatory process7 as was already proposed by Virchow8 and later by Anitschkow who noticed an "infiltrative character" of atherosclerotic lesions of cholesterol-fed animals.9
Differentiation and growth of vascular smooth muscle cells, a prerequisite of atherosclerosis progression, depends on a fine-tuned balance between activators and inhibitors of cell growth.10 In the 1980s, Libby and colleagues reported that LDL cholesterol enhances growth factor–stimulated proliferation of vascular smooth muscle cells.11 Later, it became clear that the growth-stimulating effects of LDL cholesterol also involves oxidative stress–dependent activation of mitogen-activated protein kinases.12 Oxidative stress leads to the formation of so-called oxidized phospholipids, small molecules formed from fatty acids.13,14 This oxidation of phospholipids such as phosphatylcholine, present in LDL and cell membranes, is mediated by reactive oxygen species and lipoxygenases at the sn-2 position of polyunsaturated fatty acid residues, resulting in the formation of either complete or truncated forms of oxidized phospholipids.14 Oxidation of phosphorylcholine-containing lipids, namely of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (PAPC), results in
Related Article:
Circ. Res. 2007 101: 792-801.