title: Modified LDL decreases the binding of prostaglandin E2, I2, and E1 onto monocytes in patients with peripheral vascular disease.
abstract: Recent data suggest that various eicosanoids including prostaglandins play an important regulatory role in the development of atherosclerotic lesions. Peripheral blood monocytes have been implemented in early atherogenesis because they express receptors specific for modified LDL. In this study we investigated the binding of tritium prostaglandins E2 (3H-PGE2), E1 (3H-PGE1) and I2 (3H-PGI2) onto intact peripheral monocytes isolated from 20 patients (32-71 years) with manifested ischemic peripheral vascular disease stage II according to Fontaine and compared the results with those obtained in 16 healthy volunteers (21-68 years). In control subjects, Scatchard analyses of the binding data indicated a single class of high-affinity binding sites for 3H-PGE2 (maximal binding capacity [Bmax] = 11,400 +/- 3200 sites/cell; dissociation constant [Kd] = 1.3 +/- 0.5 nmol/L) and two classes of binding sites for 3H-PGE1 (Bmax1 = 11,200 +/- 4900 sites/cell, Kd1 = 1.5 +/- 0.5 nmol/L; Bmax2 = 47,800 +/- 6100 sites/cell, Kd2 = 12.8 +/- 5.9 nmol/L) as well as for 3H-PGI2 (Bmax1 = 10,100 +/- 3700 sites/cell, Kd1 = 1.7 +/- 0.7 nmol/L; Bmax2 = 81,200 +/- 5200 sites/cell, Kd2 = 14.2 +/- 6.5 nmol/L). In the patients, an absence of the higher-affinity binding class and significantly (P < .01) fewer lower-affinity binding sites were found for each ligand (PGE2: Bmax = 6600 +/- 3600 sites/cell, Kd = 12.1 +/- 3.2 nmol/L; PGI2: Bmax = 6400 +/- 3100 sites/cell, Kd = 22.1 +/- 8.3; PGE1: Bmax = 5300 +/- 1700 sites/ cell, Kd = 20.5 +/- 7.0 nmol/L). After incubation of monocytes with modified LDL (oxidized LDL or acetylated LDL), the binding of prostaglandins was significantly (P < .01 to P < .001) decreased, whereas native VLDL, LDL, and HDL did not interfere with prostaglandin binding. Prostaglandin-induced adenosine 3'-5' cyclic monophosphate (cAMP) formation by monocytes was significantly (P < .01) lower in patients (the concentrations causing 50% elevation of basal cAMP formation [ED50] were 3.8 +/- 2.4 nmol/L for PGE2, 6.3 +/- 3.5 nmol/L for PGE1, and 5.6 +/- 4.1 nmol/L for PGI2) than in the control subjects (ED50 was 1.6 +/- 1.2 nmol/L for PGE2, 4.8 +/- 2.5 nmol/L for PGE1, and 3.1 +/- 1.4 nmol/L for PGI2). After preincubation with modified LDL, the PG-induced cAMP production by monocytes was remarkably decreased in both patients and control subjects (P < .05). Our results suggest a direct effect of modified LDL on PGE2, PGE1, and PGI2 binding onto monocytes by reducing the number of cell surface-expressed receptors available. Modified LDL also reduces the sensitivity of monocytes to prostaglandins, which results in decreased cAMP production. The complex interactions between prostaglandins and lipoproteins may play an important role during atherogenesis.
authors.affiliation: Department of Nuclear Medicine, University of Vienna, Austria.
authors.forename: S R
authors.initials: SR
authors.lastname: Li
authors.forename: Q
authors.initials: Q
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Koller
authors.forename: A
authors.initials: A
authors.lastname: Kurtaran
authors.forename: C
authors.initials: C
authors.lastname: Bischof
authors.forename: M
authors.initials: M
authors.lastname: Leimer
authors.forename: F
authors.initials: F
authors.lastname: Rauscha
authors.forename: J
authors.initials: J
authors.lastname: Pidlich
authors.forename: I
authors.initials: I
authors.lastname: Virgolini
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000527:Alprostadil / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis; D015232:Dinoprostone / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D016491:Peripheral Vascular Diseases; D012737:Sex Factors
chemical_list: D008077:Lipoproteins, LDL; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein; D011464:Epoprostenol; D000242:Cyclic AMP; D000527:Alprostadil; D015232:Dinoprostone