Key result
Homocysteine-modified LDL increases endothelial calcium and peroxynitrite while decreasing NO production and Na/K-ATPase activity.
Why the study?
The role of homocysteine-thiolactone modified LDL in altering functional properties of human endothelial cells and contributing to vascular damage was investigated.
In vitro homocysteinylation of LDL induces alterations in functional properties and NO metabolism of human endothelial cells, suggesting a mechanism for homocysteine-induced vascular damage.
Should not yet change practice; hypothesis-generating for homocysteine-mediated endothelial injury pending in vivo confirmation.
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 Ca(2+) 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 microm Hcy-thiolactone. A significant increase in cytoplasmic Ca(2+) 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 Ca(2+) content and between peroxynitrite activity and cytoplasmic Ca(2+) content. In conclusion, our results demonstrated that LDL homocysteinylated in vitro induced alterations of functional properties and NO metabolism of human endothelial cells.
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Vignini et al. (2004) studied this question. Homocysteine-thiolactone modified low-density lipoprotein (Hcy-LDL) vs. Control LDL was evaluated on Nitric oxide (NO) production, cytoplasmic Ca(2+) levels, Na(+)/K(+)-ATPase activity, and peroxynitrite production. Incubation of human aortic endothelial cells with homocysteine-modified LDL significantly increased cytoplasmic Ca(2+) and peroxynitrite production, and decreased Na(+)/K(+)-ATPase and NO production.
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