I figured some of you science nuts out there would find this interesting.
Anti-Inflammatory and Cardioprotective Activities of Synthetic High-Density Lipoprotein Containing Apolipoprotein A-I Mimetic Peptides
Monica Gomaraschi, Laura Calabresi, Giuseppe Rossoni, Stefania Iametti, Guido Franceschini, John A. Stonik, and Alan T. Remaley
Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Milan, Italy (M.G., L.C., G.F.); Molecular Disease Section, Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy (G.R.); Department of Molecular and Agroalimentary Sciences, University of Milan, Milan, Italy (S.I.); and Lipoprotein Metabolism Section, Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (J.A.S., A.T.R.)
Apolipoprotein A-I (apoA-I) mimetic peptides may represent an alternative to apoA-I for large-scale production of synthetic high-density lipoproteins (sHDL) as a therapeutic agent. In this study, the cardioprotective activity of sHDL made with either L37pA peptide or its D-stereoisomer, D37pA, was compared to sHDL made with apoA-I. The peptides were reconstituted with palmitoyl-oleoyl-phosphatidylcholine, which yielded sHDL particles comparable to apoA-I sHDL in diameter, molecular weight, and {alpha}-helical content. Pretreatment of endothelial cells with either peptide sHDL reduced tumor necrosis factor {alpha}-stimulated vascular cell adhesion molecule-1 expression to the same extent as apoA-I sHDL. In an isolated rat heart model of ischemia/reperfusion (I/R) injury, L37pA and D37pA sHDL significantly reduced postischemic cardiac contractile dysfunction compared to the saline control, as indicated by a 49.7 ± 6.4% (L37pA; P < 0.001) and 53.0 ± 9.1% (D37pA; P < 0.001) increase of left ventricular-developed pressure (LVDP) after reperfusion and by a 45.4 ± 3.4% (L37pA; P < 0.001) and 49.6 ± 2.6% (D37pA; P < 0.001) decrease of creatine kinase (CK) release. These effects were similar to the 51.3 ± 3.0% (P < 0.001) increase of LVDP and 51.3 ± 3.0 (P < 0.001) reduction of CK release induced by apoA-I sHDL. Consistent with their cardioprotective effects, all three types of sHDL particles mediated an approximate 20% (P < 0.001) reduction of cardiac tumor necrosis factor {alpha} (TNF{alpha}) content and stimulated an approximate 35% (P < 0.05) increase in postischemic release of prostacyclin. In summary, L37pA and D37pA peptides can form sHDL particles that retain a similar level of protective activity as apoA-I sHDL on the endothelium and the heart; thus, apoA-I mimetic peptides may be useful therapeutic agents for the prevention of cardiac I/R injury.
Anti-Inflammatory and Cardioprotective Activities of Synthetic High-Density Lipoprotein Containing Apolipoprotein A-I Mimetic Peptides
Monica Gomaraschi, Laura Calabresi, Giuseppe Rossoni, Stefania Iametti, Guido Franceschini, John A. Stonik, and Alan T. Remaley
Center E. Grossi Paoletti, Department of Pharmacological Sciences, University of Milan, Milan, Italy (M.G., L.C., G.F.); Molecular Disease Section, Department of Pharmacology, Chemotherapy and Medical Toxicology, University of Milan, Milan, Italy (G.R.); Department of Molecular and Agroalimentary Sciences, University of Milan, Milan, Italy (S.I.); and Lipoprotein Metabolism Section, Vascular Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland (J.A.S., A.T.R.)
Apolipoprotein A-I (apoA-I) mimetic peptides may represent an alternative to apoA-I for large-scale production of synthetic high-density lipoproteins (sHDL) as a therapeutic agent. In this study, the cardioprotective activity of sHDL made with either L37pA peptide or its D-stereoisomer, D37pA, was compared to sHDL made with apoA-I. The peptides were reconstituted with palmitoyl-oleoyl-phosphatidylcholine, which yielded sHDL particles comparable to apoA-I sHDL in diameter, molecular weight, and {alpha}-helical content. Pretreatment of endothelial cells with either peptide sHDL reduced tumor necrosis factor {alpha}-stimulated vascular cell adhesion molecule-1 expression to the same extent as apoA-I sHDL. In an isolated rat heart model of ischemia/reperfusion (I/R) injury, L37pA and D37pA sHDL significantly reduced postischemic cardiac contractile dysfunction compared to the saline control, as indicated by a 49.7 ± 6.4% (L37pA; P < 0.001) and 53.0 ± 9.1% (D37pA; P < 0.001) increase of left ventricular-developed pressure (LVDP) after reperfusion and by a 45.4 ± 3.4% (L37pA; P < 0.001) and 49.6 ± 2.6% (D37pA; P < 0.001) decrease of creatine kinase (CK) release. These effects were similar to the 51.3 ± 3.0% (P < 0.001) increase of LVDP and 51.3 ± 3.0 (P < 0.001) reduction of CK release induced by apoA-I sHDL. Consistent with their cardioprotective effects, all three types of sHDL particles mediated an approximate 20% (P < 0.001) reduction of cardiac tumor necrosis factor {alpha} (TNF{alpha}) content and stimulated an approximate 35% (P < 0.05) increase in postischemic release of prostacyclin. In summary, L37pA and D37pA peptides can form sHDL particles that retain a similar level of protective activity as apoA-I sHDL on the endothelium and the heart; thus, apoA-I mimetic peptides may be useful therapeutic agents for the prevention of cardiac I/R injury.