Limits...
The Dynamics of Oxidized LDL during Atherogenesis.

Itabe H, Obama T, Kato R - J Lipids (2011)

Bottom Line: OxLDL has many stimulatory effects on vascular cells, and the presence of OxLDL in circulating blood has been established.However, recent studies on time-course changes of OxLDL in vivo raised a possibility that OxLDL can be transferred between the lesions and the circulation.In this paper, the in vivo dynamics of OxLDL are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, Showa University School of Pharmaceutical Sciences, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

ABSTRACT
Accumulating evidence indicates that oxidized low-density lipoprotein (OxLDL) is a useful marker for cardiovascular disease. The uptake of OxLDL by scavenger receptors leads to the accumulation of cholesterol within the foam cells of atherosclerotic lesions. OxLDL has many stimulatory effects on vascular cells, and the presence of OxLDL in circulating blood has been established. According to the classical hypothesis, OxLDL accumulates in the atherosclerotic lesions over a long duration, leading to advanced lesions. However, recent studies on time-course changes of OxLDL in vivo raised a possibility that OxLDL can be transferred between the lesions and the circulation. In this paper, the in vivo dynamics of OxLDL are discussed.

No MeSH data available.


Related in: MedlinePlus

Difference between OxLDL and MM-LDL. LDL is thought to be modified in a stepwise manner during the generation of OxLDL. In the initial phase of modification, the lipid components (sky blue circle) react with oxidation reagents, resulting in radical chain reactions that produce many types of lipid oxidation products (red, brown, yellow, or dark blue circle). Then, the lipid oxidation products react with the apoB protein (blue line) to generate adducts and cross-links. Radicals can attack the apoB protein directly, resulting in oxidative changes of amino acid side chains and the cleavage of peptide bonds (orange-grey line). MM-LDL may contain lipid oxidation products without extensive protein modification, because it binds to LDL receptor rather than scavenger receptors. As modification on the apoB protein proceeds, its mobility in the agarose gel electrophoresis changes greatly, and it loses the affinity to LDL receptor, and, in turn, it becomes a ligand of scavenger receptors.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3108093&req=5

fig3: Difference between OxLDL and MM-LDL. LDL is thought to be modified in a stepwise manner during the generation of OxLDL. In the initial phase of modification, the lipid components (sky blue circle) react with oxidation reagents, resulting in radical chain reactions that produce many types of lipid oxidation products (red, brown, yellow, or dark blue circle). Then, the lipid oxidation products react with the apoB protein (blue line) to generate adducts and cross-links. Radicals can attack the apoB protein directly, resulting in oxidative changes of amino acid side chains and the cleavage of peptide bonds (orange-grey line). MM-LDL may contain lipid oxidation products without extensive protein modification, because it binds to LDL receptor rather than scavenger receptors. As modification on the apoB protein proceeds, its mobility in the agarose gel electrophoresis changes greatly, and it loses the affinity to LDL receptor, and, in turn, it becomes a ligand of scavenger receptors.

Mentions: Cell culture-dependent modification of LDL has been used to prepare “minimally modified LDL” (MM-LDL), which is one form of oxidatively modified LDL [14, 15]. The chemical modification of MM-LDL is moderate judging by increases in thiobarbituric acid-reactive substances (TBARSs) and mobility in agarose gel electrophoresis, so that MM-LDL binds to LDL receptor rather than scavenger receptors. However, MM-LDL showed strong inflammatory effects on the cells in vessel wall tissues [15–17, 50]. MM-LDL contains substantial amounts of OxPC, and OxPC is believed to be partially responsible for these biological effects [51–53]. Sandwich ELISA system that uses the anti-OxPC monoclonal antibody binds as competently to MM-LDL as to copper-induced OxLDL [54]. Circulating OxLDL may be qualitatively similar to MM-LDL, since OxLDL can escape clearance system by the scavenger receptors and is immunologically positive to measurement (Figure 3).


The Dynamics of Oxidized LDL during Atherogenesis.

Itabe H, Obama T, Kato R - J Lipids (2011)

Difference between OxLDL and MM-LDL. LDL is thought to be modified in a stepwise manner during the generation of OxLDL. In the initial phase of modification, the lipid components (sky blue circle) react with oxidation reagents, resulting in radical chain reactions that produce many types of lipid oxidation products (red, brown, yellow, or dark blue circle). Then, the lipid oxidation products react with the apoB protein (blue line) to generate adducts and cross-links. Radicals can attack the apoB protein directly, resulting in oxidative changes of amino acid side chains and the cleavage of peptide bonds (orange-grey line). MM-LDL may contain lipid oxidation products without extensive protein modification, because it binds to LDL receptor rather than scavenger receptors. As modification on the apoB protein proceeds, its mobility in the agarose gel electrophoresis changes greatly, and it loses the affinity to LDL receptor, and, in turn, it becomes a ligand of scavenger receptors.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108093&req=5

fig3: Difference between OxLDL and MM-LDL. LDL is thought to be modified in a stepwise manner during the generation of OxLDL. In the initial phase of modification, the lipid components (sky blue circle) react with oxidation reagents, resulting in radical chain reactions that produce many types of lipid oxidation products (red, brown, yellow, or dark blue circle). Then, the lipid oxidation products react with the apoB protein (blue line) to generate adducts and cross-links. Radicals can attack the apoB protein directly, resulting in oxidative changes of amino acid side chains and the cleavage of peptide bonds (orange-grey line). MM-LDL may contain lipid oxidation products without extensive protein modification, because it binds to LDL receptor rather than scavenger receptors. As modification on the apoB protein proceeds, its mobility in the agarose gel electrophoresis changes greatly, and it loses the affinity to LDL receptor, and, in turn, it becomes a ligand of scavenger receptors.
Mentions: Cell culture-dependent modification of LDL has been used to prepare “minimally modified LDL” (MM-LDL), which is one form of oxidatively modified LDL [14, 15]. The chemical modification of MM-LDL is moderate judging by increases in thiobarbituric acid-reactive substances (TBARSs) and mobility in agarose gel electrophoresis, so that MM-LDL binds to LDL receptor rather than scavenger receptors. However, MM-LDL showed strong inflammatory effects on the cells in vessel wall tissues [15–17, 50]. MM-LDL contains substantial amounts of OxPC, and OxPC is believed to be partially responsible for these biological effects [51–53]. Sandwich ELISA system that uses the anti-OxPC monoclonal antibody binds as competently to MM-LDL as to copper-induced OxLDL [54]. Circulating OxLDL may be qualitatively similar to MM-LDL, since OxLDL can escape clearance system by the scavenger receptors and is immunologically positive to measurement (Figure 3).

Bottom Line: OxLDL has many stimulatory effects on vascular cells, and the presence of OxLDL in circulating blood has been established.However, recent studies on time-course changes of OxLDL in vivo raised a possibility that OxLDL can be transferred between the lesions and the circulation.In this paper, the in vivo dynamics of OxLDL are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Chemistry, Showa University School of Pharmaceutical Sciences, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.

ABSTRACT
Accumulating evidence indicates that oxidized low-density lipoprotein (OxLDL) is a useful marker for cardiovascular disease. The uptake of OxLDL by scavenger receptors leads to the accumulation of cholesterol within the foam cells of atherosclerotic lesions. OxLDL has many stimulatory effects on vascular cells, and the presence of OxLDL in circulating blood has been established. According to the classical hypothesis, OxLDL accumulates in the atherosclerotic lesions over a long duration, leading to advanced lesions. However, recent studies on time-course changes of OxLDL in vivo raised a possibility that OxLDL can be transferred between the lesions and the circulation. In this paper, the in vivo dynamics of OxLDL are discussed.

No MeSH data available.


Related in: MedlinePlus