High-density lipoproteins neutralize C-reactive protein proinflammatory activity

• Published in: Circulation (New York, N.Y.) Vol. 109; no. 17; pp. 2116 - 2122
• Main Authors: WADHAM, Carol, ALBANESE, Nathaniel, ROBERTS, Jane, LIJUN WANG, BAGLEY, Christopher J, GAMBLE, Jennifer R, RYE, Kerry-Anne, BARTER, Philip J, VADAS, Mathew A, PU XIA
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 04.05.2004
• Subjects: Animals; Aorta; Biological and medical sciences; Blood and lymphatic vessels; C-Reactive Protein - antagonists & inhibitors; C-Reactive Protein - pharmacology; Cardiology. Vascular system; Cattle; Cell Adhesion; Cells, Cultured - drug effects; Cells, Cultured - metabolism; Culture Media, Conditioned - pharmacology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; E-Selectin - biosynthesis; E-Selectin - genetics; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Gene Expression Regulation - drug effects; Humans; Inflammation; Intercellular Adhesion Molecule-1 - biosynthesis; Intercellular Adhesion Molecule-1 - genetics; Lipoproteins, HDL - pharmacology; Liposomes - pharmacology; Medical sciences; Oxidation-Reduction; Phosphatidylcholines - pharmacology; Recombinant Proteins - pharmacology; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; U937 Cells - drug effects; Umbilical Veins; Vascular Cell Adhesion Molecule-1 - biosynthesis; Vascular Cell Adhesion Molecule-1 - genetics; Vascular disease; Atherosclerosis; protein; Cardiovascular disease; Inflammation; Lipoprotein; C reactive protein; lipoproteins
• DOI: 10.1161/01.CIR.0000127419.45975.26
• ISSN: 0009-7322

C-reactive protein (CRP), a well-recognized marker of atherosclerosis, has recently been suggested to have a direct proinflammatory effect. The constitutive expression of low levels of CRP in normal plasma suggests the likelihood that a natural factor exists to neutralize the effect of CRP. This factor(s) has not yet been identified. Method and Results- The proinflammatory effect of CRP was measured by the induction of inflammatory adhesion molecules in human umbilical vein endothelial cells (HUVECs). We show that CRP significantly induced upregulation of adhesion molecules in both protein and mRNA levels. The CRP-induced expression of these inflammatory adhesion molecules was completely suppressed when the cells were preincubated with a physiological concentration (1 mg/mL apolipoprotein A-I) of HDLs derived from human plasma (native HDL) or reconstituted HDL (rHDL) at a very low concentration (0.01 mg/mL apolipoprotein A-I). A novel mechanism of HDL inhibition is likely to operate, because (1) rHDL was 100 times more potent than native HDL, (2) preincubation with HDL and its sustained presence were obligatory, and (3) oxidized 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine was the fundamental active component. The CRP-induced upregulation of inflammatory adhesion molecules in HUVECs was completely prevented by HDL via their oxidized phospholipid components.