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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

Possible in vivo behavior of OxLDL. (a) The temporal rise and fall of plasma OxLDL levels suggest that MM-LDL (OxLDL) may be transferred between the vessel wall tissues and circulation in the early stages of atherogenesis. In this stage, circulating OxLDL is likely to be MM-LDL, since heavily oxidized LDL is very rapidly cleared from the circulation. The tissues of the vessel wall could be the site of LDL oxidation, but further study is needed to examine whether oxidation proceeds in apparently healthy vessel walls during the very early stages. When the plasma OxLDL level decreases atherosclerotic lesions appear to develop. (b) In advanced stages, many macrophages and foam cells are found in the atherosclerotic lesions. MM-LDL could be further modified to form OxLDL in the lesions. OxLDL is taken up by macrophages, and processed in the lysosomes. Some of the OxLDL is completely degraded, and a part of OxLDL is relatively resistant to proteolytic processing. Partially degraded OxLDL particles are observed in the lesions. (c) Upon plaque rupture, or when an atherosclerotic plaque is injured by PTCA treatment, OxLDL and partially degraded OxLDL are rapidly released from the lesions into the circulation, which causes a temporal rise of the plasma OxLDL level.
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fig2: Possible in vivo behavior of OxLDL. (a) The temporal rise and fall of plasma OxLDL levels suggest that MM-LDL (OxLDL) may be transferred between the vessel wall tissues and circulation in the early stages of atherogenesis. In this stage, circulating OxLDL is likely to be MM-LDL, since heavily oxidized LDL is very rapidly cleared from the circulation. The tissues of the vessel wall could be the site of LDL oxidation, but further study is needed to examine whether oxidation proceeds in apparently healthy vessel walls during the very early stages. When the plasma OxLDL level decreases atherosclerotic lesions appear to develop. (b) In advanced stages, many macrophages and foam cells are found in the atherosclerotic lesions. MM-LDL could be further modified to form OxLDL in the lesions. OxLDL is taken up by macrophages, and processed in the lysosomes. Some of the OxLDL is completely degraded, and a part of OxLDL is relatively resistant to proteolytic processing. Partially degraded OxLDL particles are observed in the lesions. (c) Upon plaque rupture, or when an atherosclerotic plaque is injured by PTCA treatment, OxLDL and partially degraded OxLDL are rapidly released from the lesions into the circulation, which causes a temporal rise of the plasma OxLDL level.

Mentions: Atherosclerotic lesions can regress under certain conditions, such as a low-fat diet regimen or treatment with a lipid-lowering drug. In human studies, increases in plasma OxLDL levels was reported in healthy volunteers fed a low-fat diet [43]. After 37 healthy women took low-fat low-vegetable diet for 5 weeks, OxPC/apoB ratio increased by 27%, while total cholesterol did not change. In MIRACL study, patients with unstable angina pectoris or AMI were treated with atorvastatin (80 mg/day) for 16 weeks. Such treatment decreased total cholesterol and total apoB but increased OxLDL levels by 9.5% [44]. These observations suggest the possibility that OxLDL could translocate between atherosclerotic lesions and circulation. The rupture of a plaque could cause the rapid release of OxLDL into the circulation, but this may not be the only way to transfer OxLDL from the lesions into circulation. According to these recent studies, without tissue damage, OxLDL may possibly be equilibrated between the plasma and tissues (Figure 2).


The Dynamics of Oxidized LDL during Atherogenesis.

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

Possible in vivo behavior of OxLDL. (a) The temporal rise and fall of plasma OxLDL levels suggest that MM-LDL (OxLDL) may be transferred between the vessel wall tissues and circulation in the early stages of atherogenesis. In this stage, circulating OxLDL is likely to be MM-LDL, since heavily oxidized LDL is very rapidly cleared from the circulation. The tissues of the vessel wall could be the site of LDL oxidation, but further study is needed to examine whether oxidation proceeds in apparently healthy vessel walls during the very early stages. When the plasma OxLDL level decreases atherosclerotic lesions appear to develop. (b) In advanced stages, many macrophages and foam cells are found in the atherosclerotic lesions. MM-LDL could be further modified to form OxLDL in the lesions. OxLDL is taken up by macrophages, and processed in the lysosomes. Some of the OxLDL is completely degraded, and a part of OxLDL is relatively resistant to proteolytic processing. Partially degraded OxLDL particles are observed in the lesions. (c) Upon plaque rupture, or when an atherosclerotic plaque is injured by PTCA treatment, OxLDL and partially degraded OxLDL are rapidly released from the lesions into the circulation, which causes a temporal rise of the plasma OxLDL level.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Possible in vivo behavior of OxLDL. (a) The temporal rise and fall of plasma OxLDL levels suggest that MM-LDL (OxLDL) may be transferred between the vessel wall tissues and circulation in the early stages of atherogenesis. In this stage, circulating OxLDL is likely to be MM-LDL, since heavily oxidized LDL is very rapidly cleared from the circulation. The tissues of the vessel wall could be the site of LDL oxidation, but further study is needed to examine whether oxidation proceeds in apparently healthy vessel walls during the very early stages. When the plasma OxLDL level decreases atherosclerotic lesions appear to develop. (b) In advanced stages, many macrophages and foam cells are found in the atherosclerotic lesions. MM-LDL could be further modified to form OxLDL in the lesions. OxLDL is taken up by macrophages, and processed in the lysosomes. Some of the OxLDL is completely degraded, and a part of OxLDL is relatively resistant to proteolytic processing. Partially degraded OxLDL particles are observed in the lesions. (c) Upon plaque rupture, or when an atherosclerotic plaque is injured by PTCA treatment, OxLDL and partially degraded OxLDL are rapidly released from the lesions into the circulation, which causes a temporal rise of the plasma OxLDL level.
Mentions: Atherosclerotic lesions can regress under certain conditions, such as a low-fat diet regimen or treatment with a lipid-lowering drug. In human studies, increases in plasma OxLDL levels was reported in healthy volunteers fed a low-fat diet [43]. After 37 healthy women took low-fat low-vegetable diet for 5 weeks, OxPC/apoB ratio increased by 27%, while total cholesterol did not change. In MIRACL study, patients with unstable angina pectoris or AMI were treated with atorvastatin (80 mg/day) for 16 weeks. Such treatment decreased total cholesterol and total apoB but increased OxLDL levels by 9.5% [44]. These observations suggest the possibility that OxLDL could translocate between atherosclerotic lesions and circulation. The rupture of a plaque could cause the rapid release of OxLDL into the circulation, but this may not be the only way to transfer OxLDL from the lesions into circulation. According to these recent studies, without tissue damage, OxLDL may possibly be equilibrated between the plasma and tissues (Figure 2).

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