The Experts below are selected from a list of 14706 Experts worldwide ranked by ideXlab platform
L. Duvillard - One of the best experts on this subject based on the ideXlab platform.
-
HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of Oxidised LDL on endothelium-dependent vasorelaxation.
Diabetologia, 2007Co-Authors: Laurence Perségol, M. Foissac, P. Gambert, Bruno Vergès, Laurent Lagrost, Anne Athias, L. DuvillardAbstract:Aims/hypothesis In healthy individuals, HDL can counteract the inhibition of vasorelaxation induced by Oxidised LDL. Several abnormalities such as increased size, glycation and decreased paraoxonase activity have been reported for HDL from type 1 diabetic patients. Thus, we hypothesised that the ability of HDL to protect vessels against impairments of vasorelaxation would be decreased in these patients.
-
Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium-dependent vasorelaxation.
Diabetologia, 2006Co-Authors: Laurence Perségol, M. Foissac, P. Gambert, Bruno Vergès, L. DuvillardAbstract:Aims/hypothesis In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL.
-
Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium-dependent
2006Co-Authors: M. Foissac, P. Gambert, L. DuvillardAbstract:Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are gly- cated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by Oxidised LDL. Results: Oxidised LDL inhibited endothelium-de- pendent vasodilation (maximal relaxation (Emax)=58.2± 14.6 vs 99.3±5.2% for incubation without any lipopro- tein, p
-
inability of hdl from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium dependent
2006Co-Authors: M. Foissac, P. Gambert, L. DuvillardAbstract:Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are gly- cated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by Oxidised LDL. Results: Oxidised LDL inhibited endothelium-de- pendent vasodilation (maximal relaxation (Emax)=58.2± 14.6 vs 99.3±5.2% for incubation without any lipopro- tein, p<0.0001). HDL from control subjects significantly reduced the inhibitory effect of Oxidised LDL on vaso- dilatation (Emax=77.6±12.9 vs 59.5±7.7%, p<0.001), whereas HDL from type 2 diabetic patients had no effect (Emax=52.4±20.4 vs 57.2±18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3±2.2 vs 3.1±1.4%, p<0.01) and was highly inversely correlated to Emax for Oxidised LDL+HDL in type 2 diabetic patients (r=�0.71, p<0.005). Conclusions/interpretation: In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endo- thelium-dependent vasorelaxation induced by Oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.
David S. Leake - One of the best experts on this subject based on the ideXlab platform.
-
P4 α-tocopherol does not inhibit low desnsity lipoprotein oxidation at lysosomal ph
Abstracts, 2018Co-Authors: Hkm Alboaklah, David S. LeakeAbstract:The oxidation of low density lipoprotein (LDL) was considered to be important in atherogenesis. It is well known that α-tocopherol protects against the oxidation of LDL by cells or copper ions, but α-tocopherol did not protect against cardiovascular disease in large clinical trials, leading some to doubt the importance of Oxidised LDL. We have previously shown that LDL is Oxidised in the lysosomes of macrophages, due to their acidic pH and presence of redox-active iron, raising the possibility that this is the main site of LDL oxidation, rather than the extracellular space of the arterial intima. We have now enriched LDL with α-tocopherol (by adding α-tocopherol to human plasma followed by the isolation of LDL by ultracentrifugation) and measured its oxidation by monitoring conjugated diene formation in a spectrophotometer set to 37°C and 234 nm. α-Tocopherol-enriched LDL was Oxidised much slower by Cu2+ (2, 5 or 20 µM) at pH 7.4, as expected, but was not protected against oxidation by these concentrations of Cu2+, Fe2+ or Fe3+ at pH 4.5 (lysosomal pH). The lack of protection of cardiovascular disease by α-tocopherol is therefore not proof that Oxidised LDL is not important in atherosclerosis, if the oxidation of LDL occurs in lysosomes. We therefore need to retest the Oxidised LDL hypothesis using antioxidatnts that accumulate in lysosomes and inhibit the oxidation of LDL at acidic pH. We thank the Iraqi Government for a PhD studentship (HKMA).
-
Ascorbate does not protect macrophages against apoptosis induced by Oxidised low density lipoprotein
Archives of biochemistry and biophysics, 2006Co-Authors: Lynda K. Harris, Giovanni E. Mann, Emilio Ruiz, Sohail Mushtaq, David S. LeakeAbstract:Apoptosis of macrophages and smooth muscle cells is observed in atherosclerotic lesions and may play an important role in the disease progression. Oxidised low density lipoprotein (LDL) is cytotoxic and induces apoptosis in a variety of cell types. We reported previously that ascorbate protects arterial smooth muscle cells from apoptosis induced by Oxidised LDL containing the peak levels of lipid hydroperoxides. We now demonstrate that macrophages undergo apoptosis when treated with this species of Oxidised LDL, as detected by increased annexin V binding and DNA fragmentation. Ascorbate treatment of macrophages did not protect against the cytotoxicity of Oxidised LDL, and modestly increased the levels of annexin V binding and DNA fragmentation. Oxidised LDL treatment also increased the expression of the antioxidant stress protein heme oxygenase-1 in macrophages; however, this increase was markedly attenuated by ascorbate pretreatment. Although apoptosis induced by Oxidised LDL was modestly promoted by ascorbate, ascorbate apparently decreased the levels of oxidative stress in macrophages, suggesting that this pro-apoptotic effect was not mediated by a pro-oxidant mechanism, but may instead have been due to intracellular protection of the apoptotic machinery by ascorbate.
-
Oxidation affects the flow-induced aggregation of low density lipoprotein and its inhibition by albumin.
Biochimica et biophysica acta, 2003Co-Authors: Roy M Talbot, David S. Leake, Jessica D Del Rio, Peter D WeinbergAbstract:We investigated whether oxidation alters the self-aggregation of low density lipoprotein (LDL) and the inhibition of such aggregation by albumin. Incubation with copper for different durations produced miLDLy, moderately, and highly Oxidised LDL (having, respectively, ca. 60, 300 and 160 nM lipid hydroperoxides/mg protein, and electrophoretic mobilities 1.2, 2.6 and 4.4 times that of native LDL). The rate of flow-induced aggregation was the same for native, miLDLy Oxidised and moderately Oxidised LDL, but decreased for highly Oxidised LDL. The inhibitory effect of albumin (40 mg/ml) on aggregation was reduced by mild oxidation and further reduced by moderate or severe oxidation. The net result of the two effects was that in the presence of albumin, moderately Oxidised LDL had the highest rate of aggregation and native the lowest. The reduction in the anti-aggregatory effect of albumin provides a new mechanism by which LDL oxidation might enhance net aggregation in vivo.
-
Mechanisms by which cysteine can inhibit or promote the oxidation of low density lipoprotein by copper.
Atherosclerosis, 2003Co-Authors: Rebecca A. Patterson, David J. Lamb, David S. LeakeAbstract:Abstract Oxidised low density lipoprotein (LDL) may play a role in atherogenesis. We have investigated some of the mechanisms by which the thiol cysteine and the disulphide cystine can influence the oxidation of LDL by copper ions. Cysteine or cystine (100 μM) inhibited the oxidation of native LDL by copper in a simple phosphate buffer. One of the mechanisms by which cysteine (or more likely its oxidation products in the presence of copper) and cystine inhibited LDL oxidation was by decreasing the binding of copper to LDL (97% inhibition). Cysteine, but not cystine, rapidly reduced Cu 2+ to Cu + . This may help to explain the antioxidant effect of cysteine as it may limit the amount of Cu 2+ that is available to convert α-tocopherol in LDL into the prooxidant α-tocopherol radical. Cysteine (but not cystine) had a prooxidant effect, however, toward partially Oxidised LDL in the presence of a low copper concentration, which may have been due to the rapid breakdown of lipid hydroperoxides in partially Oxidised LDL by Cu + generated by cysteine. To prove that cysteine can cause the rapid breakdown of lipid hydroperoxides in LDL, we enriched LDL with lipid hydroperoxides using an azo initiator in the absence of copper. Cysteine, but not cystine, increased the rate of lipid hydroperoxide decomposition to thiobarbituric acid-reactive substances (TBARS) in the presence of copper.
-
Effects of Oxidised low density lipoprotein on dendritic cells: a possible immunoregulatory component of the atherogenic micro-environment?
Cardiovascular research, 2002Co-Authors: Charles J.j Alderman, David S. Leake, Peter R Bunyard, Benjamin M. Chain, John C. Foreman, David R. KatzAbstract:Objective: The objective of this study was to explore the relationship between low density lipoprotein (LDL) and dendritic cell (DC) activation, based upon the hypothesis that reactive oxygen species (ROS)-mediated modification of proteins that may be present in local DC microenvironments could be important as mediators of this activation. Although LDL are known to be Oxidised in vivo, and taken up by macrophages during atherogenesis; their effect on DC has not been explored previously. Methods: Human DCs were prepared from peripheral blood monocytes using GM-CSF and IL-4. Plasma LDLs were isolated by sequential gradient centrifugation, Oxidised in CuSO4, and oxidation arrested to yield mild, moderate and highly Oxidised LDL forms. DCs exposed to these LDLs were investigated using combined phenotypic, functional (autologous T cell activation), morphological and viability assays. Results: Highly-Oxidised LDL increased DC HLA-DR, CD40 and CD86 expression, corroborated by increased DC-induced T cell proliferation. Both native and Oxidised LDL induced prominent DC clustering. However, high concentrations of highly-Oxidised LDL inhibited DC function, due to increased DC apoptosis. Conclusions: This study supports the hypothesis that Oxidised LDL are capable of triggering the transition from sentinel to messenger DC. Furthermore, the DC clustering–activation–apoptosis sequence in the presence of different LDL forms is consistent with a regulatory DC role in immunopathogenesis of atheroma. A sequence of initial accumulation of DC, increasing LDL oxidation, and DC-induced T cell activation, may explain why local breach of tolerance can occur. Above a threshold level, however, supervening DC apoptosis limits this, contributing instead to the central plaque core.
Won-hwan Park - One of the best experts on this subject based on the ideXlab platform.
-
curcumin inhibits tnfα induced lectin like Oxidised LDL receptor 1 lox 1 expression and suppresses the inflammatory response in human umbilical vein endothelial cells huvecs by an antioxidant mechanism
Journal of Enzyme Inhibition and Medicinal Chemistry, 2010Co-Authors: Hye-sook Lee, Min-ja Lee, Hyuck Kim, Sung-kyu Choi, Jai-eun Kim, Hyung-in Moon, Won-hwan ParkAbstract:In this study, the anti-oxidative activities of 70% ethanol extract from Curcuma aromatica Salisb. (CAS) and curcumin (CUR) were studied. The CAS extracts and CUR were both found to have a potent scavenging activity against the reactive species tested, as well as an inhibitory effect on LDL oxidation. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with tumour necrosis factor α (TNFα), expression of intracellular reactive oxygen species (ROS), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), lectin-like Oxidised LDL receptor-1 (LOX-1), adhesion molecules, inhibitory kappa Bα (IκBα) and nuclear factor kappa B (NFκB) were measured. In HUVECs stimulated with TNFα, CUR significantly suppressed expression of the intracellular ROS, LOX-1 and adhesion molecules, degradation of IκBα and translocation of NFκB, while inducing production of NO by phosphorylation of eNOS (p <0.05). In conclusion, CAS and CUR may modulate lipoprotein composition and attenuate oxidative stress by el...
-
Curcumin inhibits TNFα-induced lectin-like Oxidised LDL receptor-1 (LOX-1) expression and suppresses the inflammatory response in human umbilical vein endothelial cells (HUVECs) by an antioxidant mechanism
Journal of enzyme inhibition and medicinal chemistry, 2010Co-Authors: Hye-sook Lee, Min-ja Lee, Hyuck Kim, Sung-kyu Choi, Jai-eun Kim, Hyung-in Moon, Won-hwan ParkAbstract:In this study, the anti-oxidative activities of 70% ethanol extract from Curcuma aromatica Salisb. (CAS) and curcumin (CUR) were studied. The CAS extracts and CUR were both found to have a potent scavenging activity against the reactive species tested, as well as an inhibitory effect on LDL oxidation. Cultured human umbilical vein endothelial cells (HUVECs) were stimulated with tumour necrosis factor α (TNFα), expression of intracellular reactive oxygen species (ROS), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), lectin-like Oxidised LDL receptor-1 (LOX-1), adhesion molecules, inhibitory kappa Bα (IκBα) and nuclear factor kappa B (NFκB) were measured. In HUVECs stimulated with TNFα, CUR significantly suppressed expression of the intracellular ROS, LOX-1 and adhesion molecules, degradation of IκBα and translocation of NFκB, while inducing production of NO by phosphorylation of eNOS (p
M. Foissac - One of the best experts on this subject based on the ideXlab platform.
-
HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of Oxidised LDL on endothelium-dependent vasorelaxation.
Diabetologia, 2007Co-Authors: Laurence Perségol, M. Foissac, P. Gambert, Bruno Vergès, Laurent Lagrost, Anne Athias, L. DuvillardAbstract:Aims/hypothesis In healthy individuals, HDL can counteract the inhibition of vasorelaxation induced by Oxidised LDL. Several abnormalities such as increased size, glycation and decreased paraoxonase activity have been reported for HDL from type 1 diabetic patients. Thus, we hypothesised that the ability of HDL to protect vessels against impairments of vasorelaxation would be decreased in these patients.
-
Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium-dependent vasorelaxation.
Diabetologia, 2006Co-Authors: Laurence Perségol, M. Foissac, P. Gambert, Bruno Vergès, L. DuvillardAbstract:Aims/hypothesis In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL.
-
Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium-dependent
2006Co-Authors: M. Foissac, P. Gambert, L. DuvillardAbstract:Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are gly- cated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by Oxidised LDL. Results: Oxidised LDL inhibited endothelium-de- pendent vasodilation (maximal relaxation (Emax)=58.2± 14.6 vs 99.3±5.2% for incubation without any lipopro- tein, p
-
inability of hdl from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium dependent
2006Co-Authors: M. Foissac, P. Gambert, L. DuvillardAbstract:Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are gly- cated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by Oxidised LDL. Results: Oxidised LDL inhibited endothelium-de- pendent vasodilation (maximal relaxation (Emax)=58.2± 14.6 vs 99.3±5.2% for incubation without any lipopro- tein, p<0.0001). HDL from control subjects significantly reduced the inhibitory effect of Oxidised LDL on vaso- dilatation (Emax=77.6±12.9 vs 59.5±7.7%, p<0.001), whereas HDL from type 2 diabetic patients had no effect (Emax=52.4±20.4 vs 57.2±18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3±2.2 vs 3.1±1.4%, p<0.01) and was highly inversely correlated to Emax for Oxidised LDL+HDL in type 2 diabetic patients (r=�0.71, p<0.005). Conclusions/interpretation: In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endo- thelium-dependent vasorelaxation induced by Oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.
P. Gambert - One of the best experts on this subject based on the ideXlab platform.
-
HDL particles from type 1 diabetic patients are unable to reverse the inhibitory effect of Oxidised LDL on endothelium-dependent vasorelaxation.
Diabetologia, 2007Co-Authors: Laurence Perségol, M. Foissac, P. Gambert, Bruno Vergès, Laurent Lagrost, Anne Athias, L. DuvillardAbstract:Aims/hypothesis In healthy individuals, HDL can counteract the inhibition of vasorelaxation induced by Oxidised LDL. Several abnormalities such as increased size, glycation and decreased paraoxonase activity have been reported for HDL from type 1 diabetic patients. Thus, we hypothesised that the ability of HDL to protect vessels against impairments of vasorelaxation would be decreased in these patients.
-
Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium-dependent vasorelaxation.
Diabetologia, 2006Co-Authors: Laurence Perségol, M. Foissac, P. Gambert, Bruno Vergès, L. DuvillardAbstract:Aims/hypothesis In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are glycated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL.
-
Inability of HDL from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium-dependent
2006Co-Authors: M. Foissac, P. Gambert, L. DuvillardAbstract:Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are gly- cated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by Oxidised LDL. Results: Oxidised LDL inhibited endothelium-de- pendent vasodilation (maximal relaxation (Emax)=58.2± 14.6 vs 99.3±5.2% for incubation without any lipopro- tein, p
-
inability of hdl from type 2 diabetic patients to counteract the inhibitory effect of Oxidised LDL on endothelium dependent
2006Co-Authors: M. Foissac, P. Gambert, L. DuvillardAbstract:Aims/hypothesis: In healthy normolipidaemic and normoglycaemic control subjects, HDL are able to reverse the inhibition of vasodilation that is induced by Oxidised LDL. In type 2 diabetic patients, HDL are gly- cated and more triglyceride-rich than in control subjects. These alterations are likely to modify the capacity of HDL to reverse the inhibition of vasodilation induced by Oxidised LDL. Subjects and methods: Using rabbit aorta rings, we compared the ability of HDL from 16 type 2 diabetic patients and 13 control subjects to suppress the inhibition of vasodilation that is induced by Oxidised LDL. Results: Oxidised LDL inhibited endothelium-de- pendent vasodilation (maximal relaxation (Emax)=58.2± 14.6 vs 99.3±5.2% for incubation without any lipopro- tein, p<0.0001). HDL from control subjects significantly reduced the inhibitory effect of Oxidised LDL on vaso- dilatation (Emax=77.6±12.9 vs 59.5±7.7%, p<0.001), whereas HDL from type 2 diabetic patients had no effect (Emax=52.4±20.4 vs 57.2±18.7%, NS). HDL triglyceride content was significantly higher in type 2 diabetic patients than in control subjects (5.3±2.2 vs 3.1±1.4%, p<0.01) and was highly inversely correlated to Emax for Oxidised LDL+HDL in type 2 diabetic patients (r=�0.71, p<0.005). Conclusions/interpretation: In type 2 diabetes mellitus, the ability of HDL to counteract the inhibition of endo- thelium-dependent vasorelaxation induced by Oxidised LDL is impaired and is inversely correlated with HDL triglyceride content. These findings suggest that HDL are less atheroprotective in type 2 diabetic patients than in control subjects.
