TY - JOUR
T1 - Release and capture of bioactive oxidized phospholipids and oxidized cholesteryl esters during percutaneous coronary and peripheral arterial interventions in humans
AU - Ravandi, Amir
AU - Leibundgut, Gregor
AU - Hung, Ming Yow
AU - Patel, Mitul
AU - Hutchins, Patrick M.
AU - Murphy, Robert C.
AU - Prasad, Anand
AU - Mahmud, Ehtisham
AU - Miller, Yury I.
AU - Dennis, Edward A.
AU - Witztum, Joseph L.
AU - Tsimikas, Sotirios
N1 - Funding Information:
This study was funded by a grant from the Swiss National Science Foundation (to Dr. Leibundgut), the Fondation Leducq , and the National Institutes of Health R01-HL119828 , R01-HL093767 , P01-HL055798 , P01-HL088093 , R01-HL086559 , R01-HL081862 , U54-HL119893 (to Drs. Miller, Witztum, and Tsimikas), and U54-GM069338 (Drs. Murphy, Dennis, and Witztum). Dr. Patel is on the advisory board of The Medicines Company; and is a consultant for AngioDynamics. Dr. Miller has received an investigator-initiated grant from Merck & Co., Inc . Dr. Witztum is a consultant to Isis Pharmaceuticals, Inc. and Regulus Therapeutics Inc. Drs. Witztum and Tsimikas are named as inventors on patents and patent applications for the potential commercial use of antibodies to oxidized low-density lipoprotein held by the University of California-San Diego, and receive royalties from these positions. Dr. Tsimikas is a consultant for Isis Pharmaceuticals, Inc. Genzyme, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Thomas McIntyre, P h D, has served as Guest Editor for this paper.
PY - 2014/5/20
Y1 - 2014/5/20
N2 - 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.
AB - 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.
KW - angioplasty
KW - lipoproteins
KW - oxidized cholesteryl esters
KW - oxidized phospholipids
UR - https://www.scopus.com/pages/publications/84900530931
UR - https://www.scopus.com/pages/publications/84900530931#tab=citedBy
U2 - 10.1016/j.jacc.2014.01.055
DO - 10.1016/j.jacc.2014.01.055
M3 - Article
C2 - 24613321
AN - SCOPUS:84900530931
SN - 0735-1097
VL - 63
SP - 1961
EP - 1971
JO - Journal of the American College of Cardiology
JF - Journal of the American College of Cardiology
IS - 19
ER -