This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vignini, A. Articles by Mazzanti, L. Search for Related Content PubMed PubMed Citation Articles by Vignini, A. Articles by Mazzanti, L.

Modification Induced by Homocysteine and Low-Density Lipoprotein on Human Aortic Endothelial Cells: An In Vitro Study

Institute of Biochemistry, School of Medicine, Polytechnical Marche University, 60131 Ancona, Italy

Address all correspondence and requests for reprints to: Prof. Laura Mazzanti, Institute of Biochemistry, Università Politecnica delle Marche, Via P. Ranieri 65, 60131 Ancona, Italy. E-mail: mazzanti{at}univpm.it.

The aim of the present study was to investigate the effect exerted by low-density lipoprotein (LDL) modified by homocysteine (Hcy)-thiolactone (Hcy-LDL) on functional properties on human endothelial cells. Hcy-thiolactone, a reactive product formed in human cells from enzymatic conversion of Hcy, was hypothesized to play an important role in Hcy-induced vascular damages. Using endothelial cultured cells [human aortic endothelial cells (HAEC)] as cellular model, we evaluated nitric oxide (NO) production, cytoplasmic Ca²⁺ levels, Na⁺/K⁺-ATPase activity, and peroxynitrite production in cells incubated in the presence of control LDL or Hcy-LDL. Homocysteinylation of LDL was carried out by incubation of LDL, isolated from plasma of healthy subjects, with 100 µM Hcy-thiolactone. A significant increase in cytoplasmic Ca²⁺ levels and peroxynitrite production and a decrease in Na⁺/K⁺-ATPase and NO production in HAEC incubated with Hcy-LDL compared with HAEC incubated with control LDL were observed. Moreover, a positive correlation was found between Na⁺/K⁺-ATPase activity and cytoplasmic Ca²⁺ content and between peroxynitrite activity and cytoplasmic Ca²⁺ content. In conclusion, our results demonstrated that LDL homocysteinylated in vitro induced alterations of functional properties and NO metabolism of human endothelial cells.

This article has been cited by other articles:

				N. Akahoshi, C. Kobayashi, Y. Ishizaki, T. Izumi, T. Himi, M. Suematsu, and I. Ishii Genetic background conversion ameliorates semi-lethality and permits behavioral analyses in cystathionine {beta}-synthase-deficient mice, an animal model for hyperhomocysteinemia Hum. Mol. Genet., July 1, 2008; 17(13): 1994 - 2005. [Abstract] [Full Text] [PDF]

				H. Jakubowski Pathophysiological Consequences of Homocysteine Excess J. Nutr., June 1, 2006; 136(6): 1741S - 1749S. [Abstract] [Full Text] [PDF]