3.P.374 Oxidized low density lipoprotein and very low density lipoprotein enhance expression of MCP-1 in rabbit peritoneal exudate macrophages

AbstractThe importance of lipoproteins in the etiology of atherosclerosis is well established. Evidence is now accumulating to implicate thrombin in the pathogenesis of atherosclerosis. We have investigated whether atherogenic lipoproteins can support thrombin generation. In the absence of platelets or endothelial cells, both very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (LDL) support assembly of the prothrombinase complex and generation of thrombin. Thrombin generation (per μg of apolipoprotein) supported by VLDL was 19.4-fold greater than that supported by high-density lipoprotein (HDL), P < .00001, and 11.7-fold greater than that supported by LDL, P < .00001. Oxidation of LDL increased lipoprotein-supported thrombin generation 12-fold compared to unmodified LDL, P < .0001. We have shown that the phenomenon of lipoprotein-supported thrombin generation is mediated predominantly by specific phospholipids and is enhanced by oxidation of these phospholipids. The addition of vitamin E (α-tocopherol) markedly reduced the increase in thrombin generation observed after oxidation of LDL (822 ± 57 v 138 ± 47 nmol/L;P < .0001). These effects suggest that lipoproteins are important in the production of thrombin and that vitamin E may confer protection from the detrimental effects of lipoprotein oxidation by limiting thrombin formation. These results suggest that atherogenic lipoproteins are linked to the development of atherosclerosis in part by their capacity to support thrombin generation.

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Atherogenic Lipoproteins Support Assembly of the Prothrombinase Complex and Thrombin Generation: Modulation by Oxidation and Vitamin E

Blood ◽

10.1182/blood.v91.2.508.508_508_515 ◽

1998 ◽

Vol 91 (2) ◽

pp. 508-515 ◽

Cited By ~ 1

Author(s):

Simin Rota ◽

Nicola A. McWilliam ◽

Trevor P. Baglin ◽

Christopher D. Byrne

Keyword(s):

Endothelial Cells ◽

Vitamin E ◽

Thrombin Generation ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Oxidized Low Density Lipoprotein ◽

Lipoprotein Oxidation ◽

Prothrombinase Complex

The importance of lipoproteins in the etiology of atherosclerosis is well established. Evidence is now accumulating to implicate thrombin in the pathogenesis of atherosclerosis. We have investigated whether atherogenic lipoproteins can support thrombin generation. In the absence of platelets or endothelial cells, both very low-density lipoprotein (VLDL) and oxidized low-density lipoprotein (LDL) support assembly of the prothrombinase complex and generation of thrombin. Thrombin generation (per μg of apolipoprotein) supported by VLDL was 19.4-fold greater than that supported by high-density lipoprotein (HDL), P < .00001, and 11.7-fold greater than that supported by LDL, P < .00001. Oxidation of LDL increased lipoprotein-supported thrombin generation 12-fold compared to unmodified LDL, P < .0001. We have shown that the phenomenon of lipoprotein-supported thrombin generation is mediated predominantly by specific phospholipids and is enhanced by oxidation of these phospholipids. The addition of vitamin E (α-tocopherol) markedly reduced the increase in thrombin generation observed after oxidation of LDL (822 ± 57 v 138 ± 47 nmol/L;P < .0001). These effects suggest that lipoproteins are important in the production of thrombin and that vitamin E may confer protection from the detrimental effects of lipoprotein oxidation by limiting thrombin formation. These results suggest that atherogenic lipoproteins are linked to the development of atherosclerosis in part by their capacity to support thrombin generation.

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Decision letter for "Sestrin1 inhibits oxidized low-density lipoprotein-induced activation of NLRP3 inflammasome in macrophages in a murine atherosclerosis model"

10.1002/eji.201948427/v3/decision1 ◽

2020 ◽

Keyword(s):

Nlrp3 Inflammasome ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Oxidized Low Density Lipoprotein

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Review for "Sestrin1 inhibits oxidized low-density lipoprotein-induced activation of NLRP3 inflammasome in macrophages in a murine atherosclerosis model"

10.1002/eji.201948427/v2/review1 ◽

2020 ◽

Keyword(s):

Nlrp3 Inflammasome ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Density ◽

Oxidized Low Density Lipoprotein

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Studies on the Thromboplastic Effect of Human Plasma Lipoproteins

Thrombosis and Haemostasis ◽

10.1055/s-0038-1647942 ◽

1976 ◽

Vol 35 (01) ◽

pp. 178-185 ◽

Cited By ~ 8

Author(s):

Helena Sandberg ◽

Lars-Olov Andersson

Keyword(s):

High Density Lipoprotein ◽

Human Plasma ◽

Platelet Rich Plasma ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Plasma Lipoproteins ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Free Plasma ◽

Good Agreement

SummaryHuman plasma lipoprotein fractions were prepared by flotation in the ultracentrifuge. Addition of these fractions to platelet-rich, platelet-poor and platelet-free plasma affected the partial thromboplastin and Stypven clotting times to various degrees. Addition of high density lipoprotein (HDL) to platelet-poor and platelet-free plasma shortened both the partial thromboplastin and the Stypven time, whereas addition of low density lipoprotein and very low density lipoprotein (LDL + VLDL) fractions only shortened the Stypven time. The additions had little or no effect in platelet-rich plasma.Experiments involving the addition of anti-HDL antibodies to plasmas with different platelet contents and measuring of clotting times produced results that were in good agreement with those noted when lipoprotein was added. The relation between structure and the clot-promoting activity of various phospholipid components is discussed.

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