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

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.107.119479v1 322/2/514    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 Peterson, S. J. Articles by Abraham, N. G. Search for Related Content PubMed PubMed Citation Articles by Peterson, S. J. Articles by Abraham, N. G.

CARDIOVASCULAR

Long-Term Treatment with the Apolipoprotein A1 Mimetic Peptide Increases Antioxidants and Vascular Repair in Type I Diabetic Rats

Departments of Medicine (S.J.P.), Cardiology (A.L.K., J.A.M., W.S.A.), and Pharmacology (D.H., R.O., N.G.A.), New York Medical College, Valhalla, New York; Department of Biomedical Science, University of Brescia, Italy (F.R., L.F.R., A.S., R.R.); and Kansai Medical University, Osaka, Japan (S.I.)

Apolipoprotein A1 mimetic peptide (D-4F), synthesized from D-amino acid, enhances the ability of high-density lipoprotein to protect low-density lipoprotein (LDL) against oxidation in atherosclerotic disease. Using a rat model of type I diabetes, we investigated whether chronic use of D-4F would lead to up-regulation of heme oxygenase (HO)-1, endothelial cell marker (CD31⁺), and thrombomodulin (TM) expression and increase the number of endothelial progenitor cells (EPCs). Sprague-Dawley rats were rendered diabetic with streptozotocin (STZ) and either D-4F or vehicle was administered, by i.p. injection, daily for 6 weeks (100 µg/100 g b.wt.). HO activity was measured in liver, kidney, heart, and aorta. After 6 weeks of D-4F treatment, HO activity significantly increased in the heart and aorta by 29 and 31% (p < 0.05 and p < 0.49), respectively. Long-term D-4F treatment also caused a significant increase in TM and CD31⁺ expression. D-4F administration increased antioxidant capacity, as reflected by the decrease in oxidized protein and oxidized LDL, and enhanced EPC function and/or repair, as evidenced by the increase in EPC endothelial nitric-oxide synthase (eNOS) and prevention of vascular TM and CD31⁺ loss. In conclusion, HO-1 and eNOS are relevant targets for D-4F and may contribute to the D-4F-mediated increase in TM and CD31⁺, the antioxidant and anti-inflammatory properties, and confers robust vascular protection in this animal model of type 1 diabetes.

Address correspondence to: Dr. Nader G. Abraham, Department of Pharmacology, New York Medical College, Valhalla, NY 10595. E-mail: nader_abraham{at}nymc.edu

This article has been cited by other articles:

				S. J. Peterson, D. H. Kim, M. Li, V. Positano, L. Vanella, L. F. Rodella, F. Piccolomini, N. Puri, A. Gastaldelli, C. Kusmic, et al. The L-4F mimetic peptide prevents insulin resistance through increased levels of HO-1, pAMPK, and pAKT in obese mice J. Lipid Res., July 1, 2009; 50(7): 1293 - 1304. [Abstract] [Full Text] [PDF]

				A. Nicolai, M. Li, D. H. Kim, S. J. Peterson, L. Vanella, V. Positano, A. Gastaldelli, R. Rezzani, L. F. Rodella, G. Drummond, et al. Heme Oxygenase-1 Induction Remodels Adipose Tissue and Improves Insulin Sensitivity in Obesity-Induced Diabetic Rats Hypertension, March 1, 2009; 53(3): 508 - 515. [Abstract] [Full Text] [PDF]

				G. Sambuceti, S. Morbelli, L. Vanella, C. Kusmic, C. Marini, M. Massollo, C. Augeri, M. Corselli, C. Ghersi, B. Chiavarina, et al. Diabetes Impairs the Vascular Recruitment of Normal Stem Cells by Oxidant Damage, Reversed by Increases in pAMPK, Heme Oxygenase-1, and Adiponectin Stem Cells, February 1, 2009; 27(2): 399 - 407. [Abstract] [Full Text] [PDF]

				V. K. Mishra, M. N. Palgunachari, N. R. Krishna, J. Glushka, J. P. Segrest, and G. M. Anantharamaiah Effect of Leucine to Phenylalanine Substitution on the Nonpolar Face of a Class A Amphipathic Helical Peptide on Its Interaction with Lipid: HIGH RESOLUTION SOLUTION NMR STUDIES OF 4F-DIMYRISTOYLPHOSPHATIDYLCHOLINE DISCOIDAL COMPLEX J. Biol. Chem., December 5, 2008; 283(49): 34393 - 34402. [Abstract] [Full Text] [PDF]

				B. J. Van Lenten, A. C. Wagner, C.-L. Jung, P. Ruchala, A. J. Waring, R. I. Lehrer, A. D. Watson, S. Hama, M. Navab, G. M. Anantharamaiah, et al. Anti-inflammatory apoA-I-mimetic peptides bind oxidized lipids with much higher affinity than human apoA-I J. Lipid Res., November 1, 2008; 49(11): 2302 - 2311. [Abstract] [Full Text] [PDF]

				S. J. Peterson, G. Drummond, D. H. Kim, M. Li, A. L. Kruger, S. Ikehara, and N. G. Abraham L-4F treatment reduces adiposity, increases adiponectin levels, and improves insulin sensitivity in obese mice J. Lipid Res., August 1, 2008; 49(8): 1658 - 1669. [Abstract] [Full Text] [PDF]

				N. G. Abraham and A. Kappas Pharmacological and Clinical Aspects of Heme Oxygenase Pharmacol. Rev., March 1, 2008; 60(1): 79 - 127. [Abstract] [Full Text] [PDF]

				B. J. Van Lenten, A. C. Wagner, M. Navab, G. M. Anantharamaiah, S. Hama, S. T. Reddy, and A. M. Fogelman Lipoprotein inflammatory properties and serum amyloid A levels but not cholesterol levels predict lesion area in cholesterol-fed rabbits J. Lipid Res., November 1, 2007; 48(11): 2344 - 2353. [Abstract] [Full Text] [PDF]