Amir Ravandi1, Gregor Leibundgut2, Ming-Yow Hung3, Mitul Patel4, Patrick M Hutchins5, Robert C Murphy5, Anand Prasad6, Ehtisham Mahmud4, Yury I Miller4, Edward A Dennis7, Joseph L Witztum4, Sotirios Tsimikas8. 1. St. Boniface Hospital Research Centre, University of Manitoba, Winnipeg, Manitoba, Canada; Department of Medicine, University of California-San Diego, La Jolla, California. 2. Department of Medicine, University of California-San Diego, La Jolla, California; University of Basel, Basel, Switzerland. 3. Department of Medicine, University of California-San Diego, La Jolla, California; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. 4. Department of Medicine, University of California-San Diego, La Jolla, California. 5. Department of Pharmacology, University of Colorado Denver, Aurora, Colorado. 6. Department of Medicine, University of California-San Diego, La Jolla, California; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas. 7. Department of Pharmacology and Chemistry and Biochemistry, University of California, La Jolla, California. 8. Department of Medicine, University of California-San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.
Abstract
OBJECTIVES: This study sought to assess whether oxidized lipids are released downstream from obstructive plaques after percutaneous coronary and peripheral interventions using distal protection devices. BACKGROUND: Oxidation of lipoproteins generates multiple bioactive oxidized lipids that affect atherothrombosis and endothelial function. Direct evidence of their role during therapeutic procedures, which may result in no-reflow phenomenon, myocardial infarction, and stroke, is lacking. METHODS: The presence of specific oxidized lipids was assessed in embolized material captured by distal protection filter devices during uncomplicated saphenous vein graft, carotid, renal, and superficial femoral artery interventions. The presence of oxidized phospholipids (OxPL) and oxidized cholesteryl esters (OxCE) was evaluated in 24 filters using liquid chromatography, tandem mass spectrometry, enzyme-linked immunosorbent assays, and immunostaining. RESULTS: Phosphatidylcholine-containing OxPL, including (1-palmitoyl-2-[9-oxo-nonanoyl] PC), representing a major phosphatidylcholine-OxPL molecule quantitated within plaque material, [1-palmitoyl-2-(5-oxo-valeroyl)-sn-glycero-3-phosphocholine], and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine, were identified in the extracted lipid portion from all vascular beds. Several species of OxCE, such as keto, hydroperoxide, hydroxy, and epoxy cholesteryl ester derivatives from cholesteryl linoleate and cholesteryl arachidonate, were also present. The presence of OxPL was confirmed using enzyme-linked immunoassays and immunohistochemistry of captured material. CONCLUSIONS: This study documents the direct release and capture of OxPL and OxCE during percutaneous interventions from multiple arterial beds in humans. Entrance of bioactive oxidized lipids into the microcirculation may mediate adverse clinical outcomes during therapeutic procedures.
OBJECTIVES: This study sought to assess whether oxidized lipids are released downstream from obstructive plaques after percutaneous coronary and peripheral interventions using distal protection devices. BACKGROUND: Oxidation of lipoproteins generates multiple bioactive oxidized lipids that affect atherothrombosis and endothelial function. Direct evidence of their role during therapeutic procedures, which may result in no-reflow phenomenon, myocardial infarction, and stroke, is lacking. METHODS: The presence of specific oxidized lipids was assessed in embolized material captured by distal protection filter devices during uncomplicated saphenous vein graft, carotid, renal, and superficial femoral artery interventions. The presence of oxidized phospholipids (OxPL) and oxidized cholesteryl esters (OxCE) was evaluated in 24 filters using liquid chromatography, tandem mass spectrometry, enzyme-linked immunosorbent assays, and immunostaining. RESULTS:Phosphatidylcholine-containing OxPL, including (1-palmitoyl-2-[9-oxo-nonanoyl] PC), representing a major phosphatidylcholine-OxPL molecule quantitated within plaque material, [1-palmitoyl-2-(5-oxo-valeroyl)-sn-glycero-3-phosphocholine], and 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine, were identified in the extracted lipid portion from all vascular beds. Several species of OxCE, such as keto, hydroperoxide, hydroxy, and epoxy cholesteryl ester derivatives from cholesteryl linoleate and cholesteryl arachidonate, were also present. The presence of OxPL was confirmed using enzyme-linked immunoassays and immunohistochemistry of captured material. CONCLUSIONS: This study documents the direct release and capture of OxPL and OxCE during percutaneous interventions from multiple arterial beds in humans. Entrance of bioactive oxidized lipids into the microcirculation may mediate adverse clinical outcomes during therapeutic procedures.
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