Plasma kinetics of an LDL-like non-protein nanoemulsion and transfer of lipids to high-density lipoprotein (HDL) in patients with rheumatoid arthritis

• Published in: Journal of clinical lipidology Vol. 9; no. 1; pp. 72 - 80
• Main Authors: Pozzi, Fernanda S., PhD, Maranhão, Raul C., MD, PhD, Guedes, Lissiane K., MD, PhD, Borba, Eduardo F., MD, PhD, Laurindo, Ieda M.M., MD, PhD, Bonfa, Eloisa, MD, PhD, Vinagre, Carmen G., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 2015
• Subjects: Adult; Aged; Apolipoproteins B - metabolism; Arthritis, Rheumatoid - diagnosis; Arthritis, Rheumatoid - drug therapy; Carbon Radioisotopes - chemistry; Cardiovascular; Cholesterol; Cholesterol - administration & dosage; Cholesterol - chemistry; Cholesterol Esters - administration & dosage; Cholesterol Esters - chemistry; Cholesterol, HDL - blood; Cholesterol, LDL - blood; Emulsions - chemistry; Female; Humans; Injections, Intravenous; Kinetics; LDL metabolism; Lipids - blood; Lipoproteins; Lipoproteins, HDL - blood; Lipoproteins, LDL - blood; Male; Middle Aged; Nanoparticles; Nanostructures - chemistry; Rheumatoid arthritis; Transfer proteins; Treatment Outcome; Triglycerides - blood; Tritium - chemistry; Nanoparticles; LDL metabolism; Lipoproteins; Transfer proteins; Rheumatoid arthritis; Cholesterol
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2014.10.004

Background Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with cardiovascular risk, but with normal plasma lipids. Objective The aim was to investigate low-density lipoprotein (LDL) and high-density lipoprotein (HDL) metabolism in RA patients using radioactive nanoemulsions resembling an LDL lipid structure (LDE) as metabolic probes. Methods Thirty patients with RA, 16 in remission and 14 in high activity, and 30 healthy controls were studied. LDE labeled with14 C-cholesteryl ester (14 C-CE) and3 H-unesterified cholesterol (3 H-UC) was intravenously injected followed by 24—hour plasma sampling. Fractional clearance rates (FCR, h−1 ) were calculated by compartmental analysis. Lipid transfers to HDL were assayed by incubating plasma samples with a donor nanoemulsion labeled with radioactive lipids; % lipids transferred to HDL were quantified after chemical precipitation. Results LDL cholesterol, triglycerides, unesterified cholesterol, and oxidized LDL were equal in RA and controls, and HDL cholesterol was even higher in RA. Compared with controls, apolipoprotein B was lower, apolipoprotein A1 was equal, and apolipoprotein E was higher in RA. Decay curves of LDE labels were faster in RA patients than in controls (14 C-CE: 0.072 ± 0.066 and 0.038 ± 0.027, P  = .0115;3 H-UC: 0.066 ± 0.042 and 0.035 ± 0.039; P  < .0044). FCRs were equal in 2 RA subgroups. Transfer of UC, triglycerides, and phospholipids to HDL was equal between RA and controls, but CE transfer was lower in RA. HDL size was smaller in RA patients than in controls (8.5 ± 0.5 nm; 9.2 ± 0.8 nm, P  < .0001). Conclusion RA patients were more efficient in removing atherogenic LDL from plasma, as indicated by higher CE and UC FCR, with in lower apolipoprotein B. This was unexpected because of the higher cardiovascular risk in RA.