COMMENTC-reactive protein: a central player in atherogenesis or an epiphenomenon?

Atherosclerosis bears many hallmarks of a chronic inflammatory disease, and at every stage of its evolution is characterized by macrophage and T-lymphocyte infiltration [1]. The possible stimuli to this inflammatory process include oxidized low-density lipoprotein (LDL), homocysteine, free radicals generated from cigarette smoking and infectious micro-organisms. If the original insult is not adequately neutralized the inflammation may persist, causing the local and systemic release of growth factors and cytokines. These can, in turn, lead to intimal thickening by stimulating smooth-muscle cell migration, proliferation and extracellular matrix elaboration. The release of interleukin-1b and interleukin-6 from activated leucocytes may also lead to an induction of hepatic C-reactive protein (CRP) synthesis.

[1]  B. Fagerberg,et al.  Relationship between C-reactive protein and intima-media thickness in the carotid and femoral arteries and to antibodies against oxidized low-density lipoprotein in healthy men: the Atherosclerosis and Insulin Resistance (AIR) study. , 2001, Clinical science.

[2]  G. Lowe,et al.  Lipoprotein-Associated Phospholipase A2as an Independent Predictor of Coronary Heart Disease , 2000 .

[3]  A. Siegbahn,et al.  Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease. , 2000, The New England journal of medicine.

[4]  W. Koenig,et al.  C-Reactive Protein in the Arterial Intima: Role of C-Reactive Protein Receptor–Dependent Monocyte Recruitment in Atherogenesis , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[5]  J. Connell,et al.  Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease. , 2000, Clinical science.

[6]  M. Visser,et al.  Elevated C-reactive protein levels in overweight and obese adults. , 1999, JAMA.

[7]  A. Hofman,et al.  Associations of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[8]  W. Cliff,et al.  Coronary C-reactive protein distribution: its relation to development of atherosclerosis. , 1999, Atherosclerosis.

[9]  W. Koenig,et al.  C-reactive protein frequently colocalizes with the terminal complement complex in the intima of early atherosclerotic lesions of human coronary arteries. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[10]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[11]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[12]  S. Thompson,et al.  Production of C-reactive protein and risk of coronary events in stable and unstable angina , 1997, The Lancet.

[13]  L. Kuller,et al.  Relation of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Multiple Risk Factor Intervention Trial. , 1996, American journal of epidemiology.

[14]  M. Davies,et al.  Risk of thrombosis in human atherosclerotic plaques: role of extracellular lipid, macrophage, and smooth muscle cell content. , 1993, British heart journal.

[15]  J L Witztum,et al.  Antisera and monoclonal antibodies specific for epitopes generated during oxidative modification of low density lipoprotein. , 1990, Arteriosclerosis.

[16]  C. Hamilton.  Low-density lipoprotein and oxidised low-density lipoprotein: their role in the development of atherosclerosis. , 1997, Pharmacology & therapeutics.