Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Matsunaga, T. et al.

Matsunaga, Iguchi, Nakajima, Koyama, Miyazaki, Inoue, Kawai, Katayama, Hirano, Hokari, Komoda,

Glycated high-density lipoprotein induces apoptosis of endothelial cells via a mitochondrial dysfunction.

Glycation of plasma proteins may contribute to an excess risk of developing atherosclerosis in patients with diabetes mellitus. Although it is believed that high-density lipoprotein (HDL) is nonenzymatically glycosylated at an increased level in diabetic individuals, little is known about a possible linkage between glycated HDL and endothelium dysfunction in diabetes. This study set out to clarify whether glucose-modified HDL affects the function of endothelial cells by examining the apoptosis of cultured human aortic endothelial cells (HAECs) exposed to a glycated-oxidized HDL (gly-ox-HDL) prepared in vitro. Incubation of HAECs with 100 microg/ml of gly-ox-HDL for 48 h showed apoptotic features, such as cell shrinkage, membrane blebbing, and concentration and fragmentation of the nucleus, and the degree of apoptosis was dose-dependent on the glucose used in the preparation of gly-ox-HDL. Stimulation of HAECs with gly-ox-HDL elicited a marked increase in caspase 3 activity and the expressions of active caspase 3 and caspase 9, whereas concomitant treatment with a caspase 3 inhibitor significantly blocked gly-ox-HDL-induced apoptosis of HAECs. The release of cytochrome c into cytosols markedly increased in HAECs during the treatment with gly-ox-HDL. The increased expressions of Bax and Bad were detected in HAECs incubated for 24 h with gly-ox-HDL, but gly-ox-HDL failed to interfere with the expression of Bcl-2 and Bcl-x. Moreover, in vitro experiments with HDL (gly-HDL) glycated in the presence of 2 mM EDTA and Cu(2+)-oxidized HDL suggested that the apoptotic effect of gly-ox-HDL on endothelial cells might be due to an additional oxidative modification of gly-HDL. Taken altogether, additional oxidation of HDL under hyperglycemic conditions may induce endothelial apoptosis through a mitochondrial dysfunction, following the deterioration of vascular function.[1]

References

Glycated high-density lipoprotein induces apoptosis of endothelial cells via a mitochondrial dysfunction. Matsunaga, T., Iguchi, K., Nakajima, T., Koyama, I., Miyazaki, T., Inoue, I., Kawai, S., Katayama, S., Hirano, K., Hokari, S., Komoda, T. Biochem. Biophys. Res. Commun. (2001) [Pubmed]

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