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CARDIOVASCULAR

Synthetic High-Density Lipoproteins Exert Cardioprotective Effects in Myocardial Ischemia/Reperfusion Injury

Center E. Grossi Paoletti (M.G., C.R.S., G.F., L.C.), Departments of Pharmacological Sciences (G.R.) and Pharmacology, Chemotherapy, and Medical Toxicology (G.R., F.B.), University of Milano, Italy

Human high-density lipoproteins (HDLs) protect the heart against ischemia/reperfusion injury. In the present study, the cardioprotective effects of synthetic high-density lipoproteins (sHDLs) made of phosphatidylcholine and apolipoprotein A-I were investigated in isolated rat hearts, which underwent a 20-min low-flow ischemia followed by a 30-min reperfusion. The administration of sHDL during the 10 min immediately before ischemia caused a rapid, dose-dependent improvement of postischemic cardiac function: at the maximum dose (2.0 mg of sHDL protein/ml), left ventricular developed pressure (LVDP) recovered to 71.0 ± 3.2 versus 40.5 ± 3.8 mm Hg in salinetreated hearts, and coronary perfusion pressure (CPP) increased to 100.3 ± 6.2 versus 132.0 ± 9.0 mm Hg. The preservation of postischemic cardiac function was associated with a dose-dependent reduction of creatine kinase release into the coronary effluent. sHDLs administered in the first 10 min postischemia also exerted a significant, dose-dependent improvement of postischemic LVDP, CPP, and creatine kinase release, but the cardioprotective effect was less than when sHDLs were given preischemia. The preservation of postischemic cardiac function by sHDL was mediated through a reduction of cardiac tumor necrosis factor- content and an enhanced cardiac production of prostaglandin E₂ and I₂. The present experimental data indicate that sHDLs may provide a novel therapeutic approach to clinical conditions in which myocardial ischemia/reperfusion occurs, such as acute coronary syndromes, cardiac surgery, or revascularization procedures.

Address correspondence to: Prof. Guido Franceschini, Center E. Grossi Paoletti, Department of Pharmacological Sciences, via Balzaretti 9, 20133 Milano, Italy. E-mail: guido.franceschini{at}unimi.it

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