title: The catalytically active secretory phospholipase A2 type IIA is involved in restenosis development after PTCA in human coronary arteries and generation of atherogenic LDL.
abstract: Secretory phospholipase A2 type IIA (sPLA2) may actively contribute to atherogenesis, acting either within the arterial wall or in plasma. Proinflammatory eicosanoids and lysophospholipids, generated through hydrolysis of cell membrane phospho-lipids by sPLA2, initiate and prolong the inflammatory process. In the present study we examined the possible involvement of sPLA2 in development of restenosis in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). We also investigated whether serum sPLA2 could catalyze accumulation of lysophosphatidylcholine (LPC) in LDL. Concentrations and catalytic activities of sPLA2 were measured in blood serum of 49 consenting patients immediately before, 1-7 and 180 days after PTCA. All patients had repeat angiograms at 180-day follow-up. Restenosis was registered in 19 patients. Accumulation of LPC in LDL was evaluated by thin-layer chromatography after incubation of blood serum with LDL. Serum sPLA2 concentrations increased in all study patients by day 1 post-PTCA, but the increase was significantly greater and more protracted in patients who developed restenosis. Catalytic activities increased significantly 6 days post-PTCA in patients who developed restenosis, whereas for patients without restenosis there was no change in serum sPLA2 activity throughout the study period in spite of the sPLA2 presence in blood. Incubation of blood serum (6 days post-PTCA) with LDL resulted in accumulation of LPC only for those patients who subsequently developed restenosis. Manoalide, a specific inhibitor of sPLA2, completely blocked the LPC accumulation. The data indicate that elevated serum sPLA2 activity after PTCA is associated with restenosis development and may be involved in atherogenic modification of LDL in blood serum.
authors.affiliation: Cardiology Research Center, Moscow, Russia. A.Korot@cardio.ru
authors.forename: Aleksandra A
authors.initials: AA
authors.lastname: Korotaeva
authors.forename: Elena V
authors.initials: EV
authors.lastname: Samoilova
authors.forename: Aleksander I
authors.initials: AI
authors.lastname: Kaminny
authors.forename: Aleksandra A
authors.initials: AA
authors.lastname: Pirkova
authors.forename: Therese J
authors.initials: TJ
authors.lastname: Resink
authors.forename: Paul
authors.initials: P
authors.lastname: Erne
authors.forename: Nina V
authors.initials: NV
authors.lastname: Prokazova
authors.forename: Vsevolod A
authors.initials: VA
authors.lastname: Tkachuk
authors.forename: Evgeny I
authors.initials: EI
authors.lastname: Chazov
mesh_terms: D017130:Angioplasty; D015906:Angioplasty, Balloon, Coronary / Q000379:methods*; D001161:Arteriosclerosis / Q000378:metabolism*; D002384:Catalysis; D003251:Constriction, Pathologic; D017023:Coronary Angiography; D003327:Coronary Disease / Q000473:pathology; D023903:Coronary Restenosis; D003331:Coronary Vessels / Q000378:metabolism; D054501:Group II Phospholipases A2; D006801:Humans; D006868:Hydrolysis; D007249:Inflammation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism / Q000502:physiology*; D054467:Phospholipases A2; D013997:Time Factors
chemical_list: D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2