Increased activity of platelet-activating factor acetylhydrolase in low-density lipoprotein subfractions induces enhanced lysophosphatidylcholine production during oxidation in patients with heterozygous familial hypercholesterolaemia
| dc.contributor.author | Karabina, S. A. P. | en |
| dc.contributor.author | Elisaf, M. | en |
| dc.contributor.author | Bairaktari, E. | en |
| dc.contributor.author | Tzallas, C. | en |
| dc.contributor.author | Siamopoulos, K. C. | en |
| dc.contributor.author | Tselepis, A. D. | en |
| dc.date.accessioned | 2015-11-24T16:39:39Z | |
| dc.date.available | 2015-11-24T16:39:39Z | |
| dc.identifier.issn | 0014-2972 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/8178 | |
| dc.rights | Default Licence | - |
| dc.subject | familial hypercholesterolaemia | en |
| dc.subject | low-density lipoprotein subfractions | en |
| dc.subject | lysophosphatidylcholine | en |
| dc.subject | oxidation | en |
| dc.subject | platelet-activating factor acetylhydrolase | en |
| dc.subject | coronary-artery disease | en |
| dc.subject | human-plasma | en |
| dc.subject | paf-acetylhydrolase | en |
| dc.subject | endothelial-cells | en |
| dc.subject | degrading acetylhydrolase | en |
| dc.subject | lipid-peroxidation | en |
| dc.subject | cultured human | en |
| dc.subject | modified ldl | en |
| dc.subject | susceptibility | en |
| dc.subject | atherogenesis | en |
| dc.title | Increased activity of platelet-activating factor acetylhydrolase in low-density lipoprotein subfractions induces enhanced lysophosphatidylcholine production during oxidation in patients with heterozygous familial hypercholesterolaemia | en |
| heal.abstract | Patients with heterozygous familial hypercholesterolaemia (FH) have elevated plasma concentrations of low-density lipoprotein (LDL) and develop premature atherosclerosis. There is increasing evidence that oxidative modification of LDL is important for the pathogenesis of atherosclerosis, and the LDL-associated platelet-activating factor acetylhydrolase (PAF-AH) seems to play a key role in LDL oxidation by hydrolysing the oxidized phospholipids of phosphatidylcholine (PC) and producing lysophosphatidylcholine (lyso-PC). We measured the total serum and high-density lipoprotein (HDL) levels of PAF-AH activity and studied the distribution of PAF-AH activity among three LDL subfractions isolated by gradient ultracentrifugation in 15 patients with heterozygous FH and 13 normolipidaemic control subjects. We also determined the lyse-PC production in each LDL subfraction during Cu2+-induced oxidation in vitro. The total serum PAF-AH activity in heterozygous FH patients was significantly higher than in control subjects, whereas the HDL-associated PAF-AH activity, expressed as a percentage of total serum PAF-AH activity, was significantly lower in the FH patients than in control subjects (13.9 +/- 6.6% vs. 30.6 +/- 4.4%, P < 0.001). Among the LDL subfractions, the PAF-AH activity in both normolipidaemic control subjects and FH patients, expressed as nmol mg(-1) protein min(-1), was significantly higher in the LDL3 subfraction (3.31 +/- 4.8 and 53.4 +/- 11.5 respectively) than in the LDL2 (18.6 +/- 5.3 and 26.8 +/- 10.4 respectively, P < 0.0001 for both comparisons) and LDL1 subfractions (5.1 +/- 1.5 and 7.8 +/- 2.6, respectively, P < 0.0001 for both comparisons). Additionally, the enzyme activity in each LDL subfraction of the heterozygous FH patients was significantly higher than in control subjects (P < 0.02 for LDL1, P < 0.03 for LDL2 and P < 0.0001 for LDL3). No difference was observed in the susceptibility to oxidation of each LDL subfraction among the heterozygous FH patients and the normolipidaemic control subjects. During oxidation, the PAF-AH activity decreased, whereas the lyse-PC levels significantly increased in all subfractions of both groups. The lyso-PC/sphingomyelin molar ratio in each LDL subfraction of the FH patients 3 h after the onset of the oxidation was significantly higher than in control subjects [0.38 +/- 0.05 and 0.27 +/- 0.04, respectively, for LDL1 (P < 0.006), 0.47 +/- 0.08 and 0.39 +/- 0.03, respectively, for LDL2 (P < 0.04), 0.55 +/- 0.11 and 0.42 +/- 0.06, respectively, for LDL3 (P < 0.02)]. Our results show that heterozygous FH patients exhibit higher PAF-AH activity than control subjects in all LDL subfractions, resulting in higher lyso-PC production during oxidation, which confers on these subfractions higher biological potency. This phenomenon, in combination with the diminished anti-atherogenic and antioxidant capability of HDL in these patients due to the relatively low HDL-cholesterol levels compared with LDL-cholesterol levels and, consequently, the relatively low HDL-associated PAF-AH activity, could contribute to the higher atherogenicity and incidence of coronary artery disease observed in FH patients. | en |
| heal.access | campus | - |
| heal.fullTextAvailability | TRUE | - |
| heal.identifier.secondary | <Go to ISI>://A1997XL84500012 | - |
| heal.identifier.secondary | http://onlinelibrary.wiley.com/store/10.1046/j.1365-2362.1997.1570706.x/asset/j.1365-2362.1997.1570706.x.pdf?v=1&t=h0f7yesi&s=99fa2756da221c745476578a99d1dc4c587a3df2 | - |
| heal.journalName | Eur J Clin Invest | en |
| heal.journalType | peer reviewed | - |
| heal.language | en | - |
| heal.publicationDate | 1997 | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Θετικών Επιστημών. Τμήμα Χημείας | el |
| heal.type | journalArticle | - |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.type.en | Journal article | en |
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