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Minimally modified LDL is an oxidized LDL enriched with oxidized phosphatidylcholines
Hiroyuki Itabe1, Masahiro Mori, Yasuyuki Fujimoto
1Department of Molecular Pathology, Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1 Suarashi, Sagamiko, Tsukui, Kanagawa 199-0195. h-itabe@pharm.teikyo-u.ac.jp
Abstract:
The oxidative modification of low-density lipoprotein (LDL) is involved in atherogenesis. Among a variety of modified LDLs mentioned in the literature, so-called minimally modified LDL (MM-LDL) was reported to have pro-atherogenic properties despite minimal changes in its oxidative measures. After treatment of LDL with 1 micro M FeSO(4) at 4 degrees C for 96 h, the resulting MM-LDL showed a slight increase in thiobarbituric acid-reactive substances (TBARS) and little association with macrophages. On the other hand, heavily oxidized LDL, which was prepared by copper-induced oxidation of LDL at 37 degrees C, showed a sharp increase in TBARS and strong association with macrophages. By introducing a fluorometric procedure to detect aldehyde-containing phosphatidylcholines (aldehyde-PCs), we examined the amounts of aldehyde-PCs in modified LDL preparations. Aldehyde-PCs increased to 23.4 pmol/ microg protein in MM-LDL, which was more than four-fold higher than in the heavily oxidized LDL. We conclude that MM-LDL is a unique type of oxidized LDL enriched with aldehyde-PCs.
Insights
Minimally modified LDL (MM-LDL), despite minor oxidative changes, is pro-atherogenic. This study reveals MM-LDL is uniquely enriched with aldehyde-phosphatidylcholines (aldehyde-PCs), a key factor in its atherogenic potential.
Area of Science:
- Biochemistry
- Cardiovascular Research
- Oxidative Stress
Background:
- Oxidative modification of low-density lipoprotein (LDL) plays a crucial role in atherogenesis.
- Minimally modified LDL (MM-LDL) exhibits pro-atherogenic properties despite subtle oxidative alterations.
Purpose of the Study:
- To investigate the specific molecular changes in MM-LDL compared to heavily oxidized LDL.
- To quantify the levels of aldehyde-containing phosphatidylcholines (aldehyde-PCs) in different LDL oxidation states.
Main Methods:
- LDL was subjected to mild oxidation (FeSO4 treatment) to create MM-LDL.
- LDL was heavily oxidized using copper-induced oxidation.
- A fluorometric assay was employed to measure aldehyde-PCs in modified LDL preparations.
Main Results:
- MM-LDL showed only a slight increase in thiobarbituric acid-reactive substances (TBARS) and minimal macrophage association.
- Heavily oxidized LDL exhibited a significant rise in TBARS and strong macrophage binding.
- Aldehyde-PCs were found at significantly higher levels (23.4 pmol/µg protein) in MM-LDL compared to heavily oxidized LDL.
Conclusions:
- MM-LDL represents a distinct form of oxidized LDL.
- MM-LDL is characterized by a substantial enrichment of aldehyde-PCs.
- Aldehyde-PCs are a key component contributing to the pro-atherogenic nature of MM-LDL.