Apolipoprotein A-I_Milano/POPC complex attenuates post-ischemic ventricular dysfunction in the isolated rabbit heart

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• 作者：Marta Marchesi ; Erin A. Booth ; Giuseppe Rossoni ; Ricardo A. Garcí ; a ; Knut R. Hill ; Cesare R. Sirtori ; Charles L. Bisgaier ; Benedict R. Lucchesi
• 关键词：Ischemia reperfusion injury ; High-density lipoproteins ; Apolipoprotein A-I_Milano ; Apolipoprotein A-I ; Antioxidant
• 刊名：Atherosclerosis
• 出版年：2008
• 期刊代码：28_00219150
• 类别：med
• 出版时间：April 2008
• 卷：197
• 期：2
• 页码：572-578
• 文件大小：754 K

摘要

Irreversible myocardial injury is a potential consequence of coronary artery revascularization. Reperfusion leads to the production of oxidized products that can damage myocardium. High-density lipoproteins (HDL) are effective at removing oxidized lipids. We hypothesized that a synthetic HDL preparation, comprising recombinant apolipoprotein A-I_Milano (apoA-I_M) complexed with 1-palmitoyl-2-oleoyl phosphatidylcholine (POPC) (apoA-I_M/POPC) would protect the heart from reperfusion injury. The ex vivo model consisted of rabbit hearts perfused by the Langendorff method. Hearts were equilibrated with Krebs–Henseleit buffer (10 min), pretreated with either apoA-I_M/POPC (0.45 mg/mL) or vehicle (10 min), subjected to global ischemia (30 min) and reperfused for 60 min. ApoA-I_M/POPC (n = 7) prevented the left ventricular end-diastolic pressure elevation observed in the vehicle group (n = 6) at the end of reperfusion (p < 0.05). During reperfusion, coronary artery perfusion pressure increased in the controls (p < 0.001), but not with apoA-I_M/POPC. ApoA-I_M/POPC reduced the release of creatine kinase at the end of the ischemic period (p < 0.001). It also reduced cardiac left ventricle muscle lipid hydroperoxides by 46%(p < 0.05). Direct comparison of the antioxidant potential indicated that recombinant apoA-I_M was much more potent than apoA-I in attenuating low-density lipoprotein oxidation. Electron microscopy showed that apoA-I_M/POPC prevented mitochondrial granulation, disorganization and sarcomere contraction band formation indicative of reperfusion injury.