PMID- 11785781 OWN - NLM STAT- MEDLINE DCOM- 20020627 LR - 20191105 IS - 1098-8823 (Print) IS - 1098-8823 (Linking) VI - 66 IP - 4 DP - 2001 Dec TI - Oxidized low density lipoprotein inhibits prostacyclin generation by rat aorta in vitro: a key role of lysolecithin. PG - 283-304 AB - The objective of this study was to examine the effect of oxLDL on prostacyclin (PGI2) generation by rat aortic segments and to see whether the lipid fraction of oxLDL or its components are responsible for that effect. We also tested if antioxidants have any protective role. LDL oxidized by copper was characterized by higher TBARS, conjugated diene, lysophosphatidylcholine (lyso PC), oxysterols and less polyunsaturated fatty acids (PUFA) than nLDL. Preincubation of aortas with oxLDL caused a significant inhibition of PGI2 generation compared to aortas preincubated with nLDL or buffer only. The percent inhibition was dependent on the concentration of oxLDL. Most of the inhibitory effect of oxLDL resided in its lipid moiety while the lipid fraction of nLDL, as well as native LDL had no effect. Preincubation of aortas with 10 microg/ml of 7-ketocholesterol the major oxysterol in oxLDL reduced the amount of PGI2 generated by aorta at all times tested; however that decrease did not reach a significant level. Aortas preincubated with 10 microg/ml of lyso PC showed a 21-36% inhibition of PGI2 generation which was comparable to the inhibition produced by preincubating the aortas with 50 microg protein/ml of oxLDL (containing about 7.5 microg lyso PC). This indicated that most of the inhibitory effect of oxLDL was due to its lyso PC. The small molecular weight fraction (< 10 kDa) with a high level of TBARS (TBARS solution) also significantly decreased the PGI2 generation by aorta. Addition of superoxide dismutase (SOD) + catalase or vitamin E simultaneously with oxLDL or TBARS solution in the preincubation medium did not reverse their inhibitory effects. This indicated that oxygen free radicals are not a contributing factor to the inhibitory effect of oxLDL but lyso PC and the lipid peroxides and probably other components already present within oxLDL are the important inhibitors. FAU - Mahfouz, M AU - Mahfouz M AD - University of Illinois, Burnsides Research Laboratory, Urbana 61801, USA. FAU - Kummerow, F AU - Kummerow F LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Prostaglandins Other Lipid Mediat JT - Prostaglandins & other lipid mediators JID - 9808648 RN - 0 (Antioxidants) RN - 0 (Ketocholesterols) RN - 0 (Lipoproteins, LDL) RN - 0 (Lysophosphatidylcholines) RN - 0 (Solutions) RN - 0 (Thiobarbituric Acid Reactive Substances) RN - 1406-18-4 (Vitamin E) RN - DCR9Z582X0 (Epoprostenol) RN - EC 1.11.1.6 (Catalase) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - O7676FE78M (7-ketocholesterol) SB - IM MH - Animals MH - Antioxidants/metabolism MH - Aorta/drug effects/*metabolism MH - Catalase/metabolism MH - Epoprostenol/*metabolism MH - Humans MH - In Vitro Techniques MH - Ketocholesterols/pharmacology MH - Lipoproteins, LDL/chemistry/metabolism/*pharmacology MH - Lysophosphatidylcholines/*pharmacology MH - Oxidation-Reduction MH - Rats MH - Solutions MH - Superoxide Dismutase/drug effects/metabolism MH - Thiobarbituric Acid Reactive Substances/pharmacology MH - Vitamin E/pharmacology EDAT- 2002/01/12 10:00 MHDA- 2002/06/28 10:01 CRDT- 2002/01/12 10:00 PHST- 2002/01/12 10:00 [pubmed] PHST- 2002/06/28 10:01 [medline] PHST- 2002/01/12 10:00 [entrez] AID - S0090-6980(01)00166-6 [pii] AID - 10.1016/s0090-6980(01)00166-6 [doi] PST - ppublish SO - Prostaglandins Other Lipid Mediat. 2001 Dec;66(4):283-304. doi: 10.1016/s0090-6980(01)00166-6.