Apolipoprotein A-I-dependent cholesterol esterification in patients with rheumatoid arthritis.
Growing evidence suggests that atherogenesis is associated with inflammation or defective removal of cholesterol excess from peripheral cells. Apolipoprotein A-I [ApoA-I] activates the enzyme Lecithin-Cholesterol Acyl-Transferase to esterify cell cholesterol for transport to liver. Haptoglobin [Hpt] was previously found able to bind ApoA-I, and suggested to reduce the enzyme activation. The aim of this study was to demonstrate that enhanced levels of Hpt, as present during inflammation, are associated with low enzyme activity and increased thickness of the arterial wall. Enzyme activity and Hpt concentration were analysed in patients with rheumatoid arthritis having the same plasma levels of antioxidants (ascorbate, urate, alpha-tocopherol, retinol) or oxidation markers (nitrotyrosine, lipoperoxide) of healthy subjects. Cholesterol esterification, determined as ratio of cholesteryl esters with cholesterol in high-density lipoproteins, was lower in patients than in controls, and negatively correlated with the intima-media wall thickness of the common carotid. The ratio of Hpt with ApoA-I was negatively correlated with the enzyme activity, while positively correlated with intima-media wall thickness. The results suggest that high Hpt levels might severely impair the enzyme activity, thus contributing to cholesterol accumulation in vascular cells, and lesion formation in the endothelium.
Cigliano
Luisa
L
Dipartimento di Fisiologia Generale ed Ambientale, Università di Napoli Federico II, via Mezzocannone 8, Napoli-80134, Italia.
Spagnuolo
Maria Stefania
MS
Cuomo
Giovanna
G
Valentini
Gabriele
G
Niglio
Alferio
A
Abrescia
Paolo
P
D000975:Antioxidants / Q000032:analysis; D016632:Apolipoprotein A-I / Q000097:blood / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D004789:Enzyme Activation; D004951:Esterification; D006242:Haptoglobins / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D010084:Oxidation-Reduction; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism*; D017539:Tunica Intima / Q000473:pathology
D000975:Antioxidants; D016632:Apolipoprotein A-I; D006242:Haptoglobins; D002784:Cholesterol; D007862:Phosphatidylcholine-Sterol O-Acyltransferase