학술논문
Reduction of myocardial ischaemia-reperfusion injury by inactivating oxidized phospholipids.
Document Type
article
Author
Yeang, Calvin; Hasanally, Devin; Que, Xuchu; Hung, Ming-Yow; Stamenkovic, Aleksandra; Chan, David; Chaudhary, Rakesh; Margulets, Victoria; Edel, Andrea L; Hoshijima, Masahiko; Gu, Yusu; Bradford, William; Dalton, Nancy; Miu, Phuong; Cheung, David Yc; Jassal, Davinder S; Pierce, Grant N; Peterson, Kirk L; Kirshenbaum, Lorrie A; Witztum, Joseph L; Tsimikas, Sotirios; Ravandi, Amir
Source
Cardiovascular Research. 115(1)
Subject
Language
Abstract
Aims:Myocardial ischaemia followed by reperfusion (IR) causes an oxidative burst resulting in cellular dysfunction. Little is known about the impact of oxidative stress on cardiomyocyte lipids and their role in cardiac cell death. Our goal was to identify oxidized phosphatidylcholine-containing phospholipids (OxPL) generated during IR, and to determine their impact on cell viability and myocardial infarct size. Methods and results:OxPL were quantitated in isolated rat cardiomyocytes using mass spectrophotometry following 24 h of IR. Cardiomyocyte cell death was quantitated following exogenously added OxPL and in the absence or presence of E06, a 'natural' murine monoclonal antibody that binds to the PC headgroup of OxPL. The impact of OxPL on mitochondria in cardiomyocytes was also determined using cell fractionation and Bnip expression. Transgenic Ldlr-/- mice, overexpressing a single-chain variable fragment of E06 (Ldlr-/--E06-scFv-Tg) were used to assess the effect of inactivating endogenously generated OxPL in vivo on myocardial infarct size. Following IR in vitro, isolated rat cardiomyocytes showed a significant increase in the specific OxPLs PONPC, POVPC, PAzPC, and PGPC (P