228
Valdiuielso
Objective:
To analyse subclinical atherosclerotic disease by non-invasive in women with systemic lupus erythematosus. Methods: We have included 28 lupus patients without clinical manifestations of atherosclerosis, and 23 healthy subjects with equivalent sex, race and age. Clinical, anthropometrical and analytical data were obtained from patients and controls. We have assessed by ultrasonography the endothelial function in the brachyal artery and the carotid intima-media thickness. Endothelial function was measured as a percent of flow mediated dilatation before and after ischemia and nitroglycerin administered sublingually. Results: We did not find significant differences between patients and controls neither in the number and size of the atheroma plaques nor carotid intima-media thickness. On the contrary, we have found that lupus patients had lesser flow-mediated dilatation after ischemia than controls (13% vs. 17%; piO.05) but not after nitroglycerin (24% vs. 26%; not significant). Conclusions: Lupus patients free from clinical manifestations of atherosclerosis have an impaired endothelial function although they have as much carotid atherosclerosis as controls. ultrasonography
I746
LIPIDS AND CAROTID ATHEROSCLEROSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): A CASE-CONTROL STUDY
F! Valdivielso’,
M. Macias’, M. Hare’ A. Fernandez-Nebro’, J.J. Gomez-Doblas' , F! Gonzalez-Santos; ‘Lipid Unit, Rheumatology and Cardiology, Hospital Clinico Uniuersitario Virgen de la Victoria and Radiology: ‘HGB Antequera, Malaga, Spain Objective:
To analyse the relationship between carotid atherosclerosis and lipid parameters in SLE patients. Methods: So far we have analysed data from 37 consecutive lupus patients and 27 healthy subjects with equivalent sex, race and age. We measured clinical and serological features of SLE, risk factors for atherosclerosis, several anthropometric parameters, plasma apolipoproteins, Lp(a), lipids and lipoproteins separated by sequential ultracentrifugation. The prevalence, number and size of atheroma plaques as well as intima-media thickness were assessed by bilateral carotid ultrasonography. Results: Prevalence of carotid plaques as well as intimo-medial thickness were similar en both groups. However, only lupus patients had three or more plaques (5 patients vs. 0 controls). In SLE patients and controls, we have found a significant correlation (piO.05) in univariate analyses between carotid intima-media thickness and age at protocol, systolic blood pressure, cholesterol-VLDL, cholesterol-LDL, triglycerides-HDL, and triglycerides-HDL3, and apolipoprotein B levels. Furthermore, among SLE patients, plaques were more frequent in those having antiphospholipid syndrome (p
THE IN VW0 IMPORTANCE OF SR-BI AND ABCAl FOR THE DEVELOPMENT OF ATHEROSCLEROTIC LESIONS AND REVERSE CHOLESTEROL TRANSPORT
T. van Berkel, .I. Spijkers, R. Out, M. Hoekstra, .I. Twisk, M. van Eck. Division of Biopharmaceutics, Leiden, The Netherlands Scavenger receptor BI (SR-BI) has been identified as a functional HDL binding protein and can mediate the selective uptake of cholesterol esters (CE) from HDL. To verify the in uiuo importance of SR-BI we have utilized SR-BI K.O. mice (provided by Dr. M. Krieger M.I.T.) and studied the extend of atherosclerosis after an atherogenic diet for 8 weeks. The diet (1% cholesterol/15% fat/O.5% cholate) increased serum cholesterol levels approx. 2-fold, in particular in the HDL fraction. Assessment of lesion formation by lipid staining of aortic cross-sections indicated small, macrophagerich lesions in the SR-BI-/mice, with only minor lipid accumulation in wildtype or heterozygous littermates (lesion area in pm’: 18200&1508 (SR-BI-/-), 4469&2036 (SR-BI+/-), 2265&1439 (SR-BI+/+)). Analysis of mRNA expression of inflammatory markers showed an induction in the aortas of SR-BI-/mice, as compared with wildtype: ICAM-1, +llO%, VCAM-1, +250%; E-selectin, +410%: and P-selectin, +230%. To quantify the in uiuo role of SR-BI in the process of selective uptake by the liver, HDL was labeled with cholesteryl ether ([3H]CEt-HDL), and injected into SR-BI (KO). The clearance of HDL-CE from the blood circulation is greatly diminished (0.043&0.004 pools/h for SR-BI K.O. mice vs. 0.106&0.004 pools/h for WT mice) while the liver uptake is greatly lowered (at 2 hrs. after injection 1.2&0.2% of the injected dose in SR-BI K.O. mice vs. 14.7&2.4%
in WT mice. Our results indicate that absence of SR-BI, hampering the flux of cholesterol from peripheral tissues to the liver, within the context of hypercholesterolemia results in vascular inflammation and atherosclerotic lesion development.
I748
POSTPRANDIAL RECRUITMENT ASSOCIATED TO ENDOTHELIAL
OF NEUTROPHILS DYSFUNCTION
IS
A.J.H.H.M. Van Oostrom, E.J.P. De Koning, T.J. Rabelink, M. Castro Cabezas. Department of Vascular Medicine, Uniuersify Medical Center Utrecht, The Netherlands Background
and Aims: Atherosclerosis is a low-grade inflammatory disease, related to lipid and glucose metabolism, involving leukocytes, leading to preclinical endothelial dysfunction. We examined postprandial leukocyte changes and flow mediated vasodilation (FMD) after different meals. Methods: Eight healthy males (age 23(2)yrs, Mean( underwent a fat (50g/m2) and glucose load (37.5g/m2), a combination of both (mixed meal) and water (250ml). Results: The fat and mixed-meals resulted in higher postprandial triglycerides compared to glucose and water (ANOVA, piO.01 for all). Free fatty acids (FFA) after the fat load were the highest (piO.01). FFA after the mixed meal were higher compared to glucose and water (piO.01). The glucose load induced the highest glucose increase (from 4.2(0.2) to 5.3(1.2)mM, p=O.O2). The fat, glucose and mixed meals induced comparable significantly impaired FMD (7710% reduction) at t=2 or 3hrs with concomitant neutrophil increases (59%, 28% and 20% at t=3hrs). Water ingestion did not affect FMD or neutrophils. The total neutrophil response after the mixed meal was not different from the other meals, after fat and glucose this response was higher than that of water (p=O.O3). Lymphocytes increased in all tests (40% at t=lO, piO.005 vs. t=O). Monocyte and erythrocyte counts did not change. Conclusion: When fat and glucose are administered together, postprandial lipemia and glycaemia are lower than when fat or glucose is given separately. However, neutrophil increment and endothelial dysfunction persists. During the postprandial phase, endothelial dysfunction induced by fat and glucose may be caused by neutrophil changes.
I749
GLUCOSE INHIBITS A FAT-MEDIATED POSTPRANDIAL C3 INCREASE BY IMPROVED FREE FATTY ACID TRAPPING
A.J.H.H.M. Van Oostrom’, H. Van Dijk’, M. Castro Cabezas’. ‘Department of Vascular Medicine, Uniuersify Medical Center Utrecht, ‘Eijkman Winkler Institute for Medical Microbiology, Infectious Diseases and Injammation, Uniuersify Medical Center Utrecht, The Netherlands Background
and Aims: Elevated fasting complement component 3 (C3) levels are associated to coronary artery disease, obesity, fasting and postprandial lipemia and insulin resistance. C3 is the precursor of adipocyte acylation-stimulating protein (ASP=C3adesArg), which originates from chylomicron-induced activation of the complement pathway. C3adesArg is involved in adipocyte free-fatty-acid (FFA) trapping. We determined plasma C3 and lipids after four different meals. Methods: Six healthy males (age 22(2)yrs, Mean( ingested a standardised 1Ohrs oral fat (50 g fat/m2 body surface) and glucose load (37.5 g&2), a combination of both and 250 ml water. Results: TG after the fat and mixed meals were higher compared to the water and glucose test (ANOVA, piO.002). Peak TG after the fat meal was higher and occurred later than after the mixed meal. FFA was lower after the mixed meal than after the fat meal (p=O.O5). Ketone bodies increased less after the mixed meal, suggesting less hepatic FFA delivery. The fat load induced a C3 increase to maximum values at T=3hrs (p=O.O3). The other meals did not show C3 changes. Conclusion: Adding glucose to an oral fat load reduces postprandial lipemia and prevents C3 increase in viva. Since C3 is involved in TG and FFA metabolism, it can be hypothesised that glucose optimises adipocyte C3-mediated postprandial FFA trapping. A mixed meal in insulin sensitive subjects contributes to a healthy lipoprotein phenotype, but may also lead to obesity due to increased peripheral FFA trapping.
73rd EAS Congress