QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.129411v1 324/2/776    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gomaraschi, M. Articles by Remaley, A. T. Search for Related Content PubMed PubMed Citation Articles by Gomaraschi, M. Articles by Remaley, A. T.

CARDIOVASCULAR

Anti-Inflammatory and Cardioprotective Activities of Synthetic High-Density Lipoprotein Containing Apolipoprotein A-I Mimetic Peptides

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 -helical content. Pretreatment of endothelial cells with either peptide sHDL reduced tumor necrosis factor -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 (TNF) 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.

Address correspondence to: Alan T. Remaley, National Institutes of Health, 10 Center Dr., Bldg. 10/Rm. 2C-433, Bethesda, MD 20892. E-mail: aremaley{at}nih.gov

This article has been cited by other articles:

				A. Mak, R. C.-M. Ho, J. Y.-S. Tan, G. G. Teng, M. Lahiri, A. Lateef, S. Vasoo, M. L. Boey, D. R. Koh, and P. H. Feng Atherogenic serum lipid profile is an independent predictor for gouty flares in patients with gouty arthropathy Rheumatology, March 1, 2009; 48(3): 262 - 265. [Abstract] [Full Text] [PDF]

				K.-A. Rye and P. J. Barter Antiinflammatory Actions of HDL: A New Insight Arterioscler. Thromb. Vasc. Biol., November 1, 2008; 28(11): 1890 - 1891. [Full Text] [PDF]