Low-density lipoprotein oxidation in essential hypertension

Maggi, E.; Marchesi, E.; Ravetta, Valentina; Falaschi, Francesco; Finardi, G; Bellomo, Giorgio

doi:10.1097/00004872-199310000-00015

Cited by 76 publications

(41 citation statements)

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“…Numerous recently published studies have employed lag-time measurements at a single copper concentration to correlate oxidation resistance of LDL with other parameters, such as severity of myocardial infarction [21], predominance of more dense LDL subclasses [22,23], anti-oxidant status [16], composition of dietary fats, [24] and various diseases [25]. Our findings clearly show that a single lag-time measurement may be misleading since a high oxidation resistance of a particular LDL can result either from a high constant K or a low radicalgenerating capacity of the bound copper (Ri _).…”

Section: Discussionmentioning

confidence: 99%

Low density lipoprotein is saturable by pro‐oxidant copper

1994

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The oxidative resistance of low density lipoprotein (LDL) can be experimentally described by the length of time during which no significant lipid peroxidation is observed in a pro-oxidant environment. This period of inhibited oxidation, termed the 'lag phase', is partially due to the radical scavenging reactions of the anti-oxidants contained in the LDL particle. We have shown that the LDL lag time decreases with increasing copper concentration, leveling out at a relatively high copper-to-LDL ratio. This behaviour demonstrates the existence of a finite number of saturable pro-oxidant copper binding sites within the LDL particle. The relationship is described by the equation, lag time = [Cu]-' . K. tti + tti where the constant, K, is the negative reciprocal of the x-axis intercept of the graphed function, and tti, is given by the y-axis intercept. By this definition of the constant, K is the amount of copper that will produce a lag time of twice tti, while tmi,, is the minimum time a particular LDL will resist oxidation at a maximum copper concentration.

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Section: Discussionmentioning

confidence: 99%

Low density lipoprotein is saturable by pro‐oxidant copper

1994

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“…20 With the exception of a few studies, the vast majority of clinical investigations of LDL oxidation have concerned the demonstration of a decreased resistance of LDL to in vitro oxidation in conditions associated with accelerated atherosclerosis, such as hypercholesterolemia, 18 coronary heart disease, 21 uremia, 22 and hypertension. 23 Moreover, since the susceptibility of LDL to oxidation depends on both the entity of prooxidant stimuli and antioxidant concentration within the LDL particle, the level of vitamin E (the most abundant antioxidant in LDL) has also often been measured. 22 - 23 An unresolved and definitely critical issue for considering the reported changes indicative of a real risk for lipoprotein oxidation is the definition of how relevant a decrease in LDL resistance to in vitro oxidation is for the oxidative modifications occurring in vivo.…”

Section: A Study Of In Vitro and In Vivo Oxidation Markersmentioning

confidence: 99%

“…23 Moreover, since the susceptibility of LDL to oxidation depends on both the entity of prooxidant stimuli and antioxidant concentration within the LDL particle, the level of vitamin E (the most abundant antioxidant in LDL) has also often been measured. 22 - 23 An unresolved and definitely critical issue for considering the reported changes indicative of a real risk for lipoprotein oxidation is the definition of how relevant a decrease in LDL resistance to in vitro oxidation is for the oxidative modifications occurring in vivo. Following such modifications, antigenic epitopes are generated and elicit an immune response.…”

Section: A Study Of In Vitro and In Vivo Oxidation Markersmentioning

confidence: 99%

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Maggi

Chiesa

Melissano

et al. 1994

Arterioscler Thromb

189

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Among the various risk factors involved in the development and progression of carotid atherosclerosis, the oxidation of LDL has been proposed to play a relevant role. LDL oxidation has been investigated in 94 patients with severe carotid atherosclerosis undergoing elective carotid artery endarterectomy and in 42 matched control subjects. LDL oxidation was evaluated in all patients as (1) the susceptibility to in vitro oxidation, (2) vitamin E concentration and its efficiency in LDL, and (3) the presence of autoantibodies against oxidatively modified lipoprotein to monitor the occurrence of the oxidative processes taking place in vivo. No difference was detected between control subjects and patients concerning vitamin E concentration and the kinetics of conjugated diene formation in isolated LDL exposed to CuSO 4 . However, vitamin E efficiency was lower (9.6±4.2 versus 30.2±7.6 min/ nmol vitamin E) and the duration of the vitamin E-independent lag phase was longer (105.5±16.5 versus 58± 11.8 minutes) in the patient group. Autoantibodies against oxidatively modified lipoproteins were measured with an ELISA method using native LDL, Cu 2+ -oxidized LDL (oxLDL), or malondialdehyde-derivatized LDL (MDA-LDL) as antigens. To monitor cross-reactivity of the antibodies detected with other C arotid atherosclerosis, ranging from intima-media thickening to the appearance of more advanced lesions such as fibrotic and complicated plaques, affects about 25% of the whole population.

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“…This enhanced susceptibility has been observed in patients with familial hypercholesterolaemia [14,15], coronary artery disease [16,17], renal failure [18,19], hypertension [20] and diabetes mellitus [21].…”

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confidence: 99%

Effects of troglitazone on in vitro oxidation of LDL and HDL induced by copper ions and endothelial cells

Cominacini

Garbin

Pastorino³

et al. 1997

Diabetologia

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Low density lipoprotein (LDL) oxidation is believed to play an important role in the development of atherosclerotic plaques [1][2][3][4][5]. This view is supported by LDL with characteristics similar to those of oxidatively modified LDL being present in atheromatous lesions [6]. Studies in cultured cells have demonstrated that oxidized LDL is chemotactic for monocytes and stimulates monocyte endothelial cell interaction [7,8]. It can also cause initial endothelial cell damage and increase uptake by scavenger receptors on macrophages, leading to cholesterol accumulation and foam cell formation [7,9].Oxidative modification of LDL is not likely to occur in circulation [3]. In view of the difficulties in identifying oxidized lipoprotein in plasma, many workers have attempted to analyse the oxidation susceptibility of isolated LDL particles in vitro [10,11]. If LDL can penetrate macrophages only after its modification [3], the ability of LDL to resist oxidation could be an Diabetologia (1997) Summary Troglitazone is a new oral antidiabetic agent able to reduce lipid peroxidation. In this study we evaluated its effect on the susceptibility of LDL and HDL to in vitro oxidation induced by copper ions and endothelial cells. In Cu ++ -induced LDL modification, different amounts of troglitazone were added to aliquots of the same pool of plasma with subsequent ultracentrifuge separation of LDL and HDL. Differences in LDL and HDL susceptibility to in vitro oxidation with Cu ++ were studied by measuring the changes in fluorescence intensity (expressed as lag phase). LDL derived from plasma incubated with different amounts of troglitazone were also incubated with umbilical vein endothelial cells (HU-VEC), the modification being monitored by LDL relative electrophoretic mobility and fluorescence. During Cu ++ -and HUVEC-induced LDL oxidation, the decay rate of vitamin E, and the potency of troglitazone as a radical scavenger in comparison with vitamin E were also studied. Troglitazone determined a significant, dose-dependent decrease in Cu ++ -induced LDL and HDL oxidation. Incubation with HUVEC was also followed by a progressive, significant decrease of LDL relative electrophoretic mobility and fluorescence intensity. During Cu ++ -and HU-VEC-induced-LDL modification, troglitazone significantly reduced the rate of vitamin E decay. In this study we also demonstrated that under the same oxidative stress, troglitazone was much more potent as a radical scavenger than vitamin E. In conclusion, the results demonstrate that troglitazone can reduce LDL and HDL in vitro oxidation and that, during this process, it can protect vitamin E. In addition to ensuring blood glucose control, the drug may therefore be useful in inhibiting lipoprotein peroxidation. [Diabetologia (1997)

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Low-density lipoprotein oxidation in essential hypertension

Cited by 76 publications

References 0 publications

Low density lipoprotein is saturable by pro‐oxidant copper

Low density lipoprotein is saturable by pro‐oxidant copper

LDL oxidation in patients with severe carotid atherosclerosis. A study of in vitro and in vivo oxidation markers.

Effects of troglitazone on in vitro oxidation of LDL and HDL induced by copper ions and endothelial cells

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