Apolipoprotein A-IMilano/POPC complex attenuates post-ischemic ventricular dysfunction in the isolated rabbit heart
Articolo
Data di Pubblicazione:
2008
Citazione:
Apolipoprotein A-IMilano/POPC complex attenuates post-ischemic ventricular dysfunction in the isolated rabbit heart / M. Marchesi, E.A. Booth, G. Rossoni, R.A. Garcia, K.R. Hill, C.R. Sirtori, C.L. Bisgaier, B.R. Lucchesi. - In: ATHEROSCLEROSIS SUPPLEMENTS. - ISSN 1567-5688. - 197:2(2008), pp. 572-578. [10.1016/j.atherosclerosis.2007.08.028]
Abstract:
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. The apoA-I(M)/POPC complex thus appears to reduce reperfusion injury under global ischemic conditions, and may therefore have therapeutic application in the reduction of myocardial ischemia.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Antioxidant; Apolipoprotein A-I; Apolipoprotein A-IMilano; High-density lipoproteins; Ischemia reperfusion injury
Elenco autori:
M. Marchesi, E.A. Booth, G. Rossoni, R.A. Garcia, K.R. Hill, C.R. Sirtori, C.L. Bisgaier, B.R. Lucchesi
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