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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 with (14)C-cholesteryl ester ((14)C-CE) and (3)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., (Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

A cholesterol-rich nanoemulsion (LDE) that mimics the composition of low-density lipoprotein (LDL) acquires apoE in the plasma and is taken-up by the cells by LDL receptors. In this study, to verify whether free cholesterol (FC) and the cholesteryl ester (CE) components of LDL are taken-up differently by the vessels. LDE labeled with (3)H-cholesterol and (14)C-cholesteryl oleate was injected into 20 coronary artery disease patients 24 h before a scheduled myocardial coronary artery bypass grafting. The plasma kinetics of both radiolabels was determined from plasma samples collected over 24 h, and fragments of vessels discarded during surgery were collected and analyzed for radioactivity. LDE FC was removed faster than CE. The radioactive counting of LDE CE was greater than that of LDE FC in the blood, but the uptake of FC was markedly greater than that of CE in all fragments: fivefold greater in the aorta (p = 0.04), fourfold greater in the internal thoracic artery (p = 0.03), tenfold greater in the saphenous vein (p = 0.01) and threefold in the radial artery (p = 0.05). In conclusion, the greater removal from plasma of FC compared with CE and the remarkably greater vessel tissue uptake of FC compared with CE suggests that, in the plasma, FC dissociates from the nanoemulsion particles and precipitates in the vessels. Considering LDE as an artificial nanoemulsion model for LDL, our results suggest that dissociation of FC from lipoprotein particles and deposition in the vessel wall may play a role as an independent mechanism in atherogenesis.

Background: Development of coronary graft disease is currently the main cause of late heart-transplantation (HT) failure. HT patients frequently show hypercholesterolemia as well as alterations in chylomicron metabolism. These postHT changes may be important in coronary graft disease development. To clarify whether hypercholesterolemia is caused by decreased low-density lipoprotein (LDL) removal from the plasma, we studied the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptor., Methods: We studied 13 HT patients and 13 healthy normolipidemic subjects paired for sex, age, and body mass index. An emulsion labeled with C-cholesteryl oleate was injected intravenously, and blood samples were collected in predetermined intervals (5 minutes, 1, 2, 4, 6, and 8 hours) to determine the radioactivity decay curves and to calculate the fractional clearance rates (FCR)., Results: The plasma level of total cholesterol, LDL cholesterol, high-density lipoprotein cholesterol, and apo B were greater in HT group than in the control group (P<0.005). FCR C-cholesteryl oleate was smaller in HT patients when compared with the control group (P=0.02)., Conclusion: The results showed that HT patients have a deficiency in the mechanisms of LDL removal from the plasma, as tested by the cholesterol-rich emulsion, and this may be important in the development of coronary graft disease.

Chylomicron catabolism in the bloodstream consists of lipolysis by lipoprotein lipase and uptake of remnants by the liver. In rats, triglyceride-rich emulsions can mimic chylomicron metabolism. To further validate this model in man, the emulsion was injected intravenously into fasting and into subjects previously fed a test fatty meal. The plasma kinetic curves of the emulsion 3H-triglyceride and 14C-cholesteryl ester were determined. The fractional clearance rate (FCR) of both labels was markedly reduced in the fed subjects (triglycerides: fed = 0.018 +/- 0.007; fasting = 0.105 +/- 0.013 min-1, P < 0.001; cholesteryl ester: fed = 0.016 +/- 0.001; fasting = 0.040 +/- 0.006 min-1; P < 0.05) indicating that the emulsion and chylomicrons generated from the testinal lipid absorption compete for the same catabolic processes, confirming the validity of the method. The emulsion was injected into 11 patients with CAD and into 11 controls. All had plasma cholesterol < 240 and triglycerides < 250 mg/dl. FCR of triglycerides was 5-fold smaller in CAD compared to controls (0.028 +/- 0.004 and 0.141 +/- 0.069 min-1, respectively, P < 0.01). FCR of cholesteryl ester was 4-fold smaller in CAD than in controls (0.015 +/- 0.004 and 0.056 +/- 0.067 min-1 respectively, P < 0.05). These results indicate that both chylomicron lipolysis and remnant removal are diminished in CAD.

Purpose: To evaluate the plasma concentration of lipoprotein (a) (Lp(a) in subjects with normal or altered coronary angiography, as a risk factor of atherosclerosis in a Brazilian population., Patients and Method: Lp(a) plasma levels were determined by radioimmunoassay in 31 subjects with normal angiography and in 131 subjects with atherosclerosis. Plasma cholesterol, triglycerides, apolipoprotein A, A1 and B were also determined as well as risk factors like systemic arterial hypertension, smoking habit, diabetes and physical activity., Results: Subjects with coronary disease had Lp(a) plasma levels of 41.9 mg/dl, compared to 23.9 mg/dl found in the normal group. Coronary artery disease risk was increased 2.3 times in those with plasma Lp(a) levels equal or above 25 mg/dl, compared to those with levels below this boundary. As to other known risk factors, only smoking habit has shown correlation with coronary artery disease., Conclusion: We confirmed the value of Lp(a) as a risk factor of coronary heart disease.