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. | en |
| dc.contributor.author | Elisaf, M. S. | 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 | 2015-11-24T19:10:54Z | |
| dc.date.available | 2015-11-24T19:10:54Z | |
| dc.identifier.issn | 0014-2972 | - |
| dc.identifier.uri | https://olympias.lib.uoi.gr/jspui/handle/123456789/20880 | |
| dc.rights | Default Licence | - |
| dc.subject | 1-Alkyl-2-acetylglycerophosphocholine Esterase | en |
| dc.subject | Adolescent | en |
| dc.subject | Adult | en |
| dc.subject | Chemical Fractionation | en |
| dc.subject | Female | en |
| dc.subject | Heterozygote | en |
| dc.subject | Humans | en |
| dc.subject | Hyperlipoproteinemia Type II/*blood/*enzymology/genetics | en |
| dc.subject | Lipoproteins, LDL/*blood/chemistry | en |
| dc.subject | Lysophosphatidylcholines/*biosynthesis/chemistry | en |
| dc.subject | Male | en |
| dc.subject | Middle Aged | en |
| dc.subject | Oxidation-Reduction | en |
| dc.subject | Phospholipases A/*blood | 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 lyso-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 (33.1 +/- 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 lyso-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 | http://www.ncbi.nlm.nih.gov/pubmed/9263748 | - |
| 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=h0m6f0vs&s=6fbef5d5012ab3ae2b6818215d02e1905bca528e | - |
| heal.journalName | Eur J Clin Invest | en |
| heal.journalType | peer-reviewed | - |
| heal.language | en | - |
| heal.publicationDate | 1997 | - |
| heal.recordProvider | Πανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικής | el |
| heal.type | journalArticle | - |
| heal.type.el | Άρθρο Περιοδικού | el |
| heal.type.en | Journal article | en |
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