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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

Stabilins, novel endothelial scavenger receptors, could have a role in the clearance of OxLDL in the liver and from circulation. Heavily oxidized LDL is taken up by Kupffer cells, whereas sinusoidal endothelial cells can take up both mildly and highly oxidized form of LDL. The novel scavenger receptors stabilin-1 and -2, which can bind to both types of OxLDL, could be involved in the process of clearing OxLDL from the circulation in the liver.
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fig4: Stabilins, novel endothelial scavenger receptors, could have a role in the clearance of OxLDL in the liver and from circulation. Heavily oxidized LDL is taken up by Kupffer cells, whereas sinusoidal endothelial cells can take up both mildly and highly oxidized form of LDL. The novel scavenger receptors stabilin-1 and -2, which can bind to both types of OxLDL, could be involved in the process of clearing OxLDL from the circulation in the liver.

Mentions: Kupffer cells, the macrophage-like cells of the liver, express scavenger receptors, including SR-A. However, it was surprising that the clearance rate of OxLDL from circulation in SR-A knockout mice was similar to that in normal mice [75]. This suggests that there might be alternative receptors or systems for the uptake of OxLDL in liver cells. Recently, Li et al. reported that both Kupffer cells and sinusoidal endothelial cells in the liver endocytose OxLDL and MM-LDL, and this process is mediated by the novel scavenger receptor stabilin-2 [76]. Stabilins, specifically stabilin-1 and stabilin-2, were initially found as receptors for hyarulonan [77, 78]; however, they were identical to FEEL-1 and FEEL-2, which are reported to be endothelial scavenger receptors [79]. These two stabilins are expressed in the sinusoidal endothelial cells of the liver but show different ligand specificities. Stabilin-1 binds to the both mildly and highly oxidized forms of LDL, while stablin-2 selectively binds to the highly oxidized LDL. When nonparenchymal cells, which contain both sinusoidal endothelial cells and Kupffer cells, were incubated with these two forms of OxLDL, the uptake of mildly oxidized form of LDL was observed only in endothelial cells, whereas both cells were capable of taking up highly oxidized LDL. The co-localization of OxLDL and stabilins has been demonstrated by immunoelectronmicrography. These observations suggest that endothelial cells might have a significant role in the metabolism of circulating modified LDL. If MM-LDL represents the circulating form of OxLDL, endothelial cells may be an important site of accumulation, metabolism, and further modification of MM-LDL (Figure 4).


The Dynamics of Oxidized LDL during Atherogenesis.

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

Stabilins, novel endothelial scavenger receptors, could have a role in the clearance of OxLDL in the liver and from circulation. Heavily oxidized LDL is taken up by Kupffer cells, whereas sinusoidal endothelial cells can take up both mildly and highly oxidized form of LDL. The novel scavenger receptors stabilin-1 and -2, which can bind to both types of OxLDL, could be involved in the process of clearing OxLDL from the circulation in the liver.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: Stabilins, novel endothelial scavenger receptors, could have a role in the clearance of OxLDL in the liver and from circulation. Heavily oxidized LDL is taken up by Kupffer cells, whereas sinusoidal endothelial cells can take up both mildly and highly oxidized form of LDL. The novel scavenger receptors stabilin-1 and -2, which can bind to both types of OxLDL, could be involved in the process of clearing OxLDL from the circulation in the liver.
Mentions: Kupffer cells, the macrophage-like cells of the liver, express scavenger receptors, including SR-A. However, it was surprising that the clearance rate of OxLDL from circulation in SR-A knockout mice was similar to that in normal mice [75]. This suggests that there might be alternative receptors or systems for the uptake of OxLDL in liver cells. Recently, Li et al. reported that both Kupffer cells and sinusoidal endothelial cells in the liver endocytose OxLDL and MM-LDL, and this process is mediated by the novel scavenger receptor stabilin-2 [76]. Stabilins, specifically stabilin-1 and stabilin-2, were initially found as receptors for hyarulonan [77, 78]; however, they were identical to FEEL-1 and FEEL-2, which are reported to be endothelial scavenger receptors [79]. These two stabilins are expressed in the sinusoidal endothelial cells of the liver but show different ligand specificities. Stabilin-1 binds to the both mildly and highly oxidized forms of LDL, while stablin-2 selectively binds to the highly oxidized LDL. When nonparenchymal cells, which contain both sinusoidal endothelial cells and Kupffer cells, were incubated with these two forms of OxLDL, the uptake of mildly oxidized form of LDL was observed only in endothelial cells, whereas both cells were capable of taking up highly oxidized LDL. The co-localization of OxLDL and stabilins has been demonstrated by immunoelectronmicrography. These observations suggest that endothelial cells might have a significant role in the metabolism of circulating modified LDL. If MM-LDL represents the circulating form of OxLDL, endothelial cells may be an important site of accumulation, metabolism, and further modification of MM-LDL (Figure 4).

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