Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta

Andrews, Helen E.; Bruckdorfer, K. Richard; Dunn, R. C.; Jacobs, Michael

doi:10.1038/327237a0

Cited by 296 publications

(95 citation statements)

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“…We have linked this observation to lowdensity lipoproteins (LDL) which at high plasma concentrations are known risk factors for coronary heart disease. In support of this claim, we have shown in our laboratory that LDL inhibit, in an irreversible manner, relaxations mediated by EDRF in rabbit aorta precontracted by noradrenaline or 5-hydroxytryptamine (Andrews et al, 1987). Furthermore, LDL-modified by oxidation, which are known to be present in the intima of atherosclerotic arteries and thought to be the atherogenic form of LDL (Yla-Herttuala et al, 1989), behaved in a similar way to that of native LDL .…”

Section: Introductionsupporting

confidence: 59%

“…To remove contaminating plasma proteins, LDL was recentrifuged for 10h in a conventional rotor at 190,000g (r = 6.75 cm) in buffer with density adjusted to 1.063gml-1 (Andrews et al, 1987). Buffers contained 0.3 mm EDTA to prevent oxidation.…”

Section: Preparation Of Lipoproteinsmentioning

confidence: 99%

“…Two mm wide, transverse rings were cut and paired tissues were mounted under a resting tension of 2g, in oxygenated Krebs-bicarbonate buffer containing 0.3mm EDTA at 370C, for isometric force measurements (Andrews et al, 1987). Tissues were equilibrated for 90min and pre-contracted with noradrenaline (NA), adrenaline (Ad), 5-hydroxytryptamine (5-HT), phenylephrine (PE) or (D Macmillan Press Ltd, 1990 prostaglandin F2a to give 75% of the maximal contraction obtained with NA.…”

Section: Measurement Of Endothelium-dependent Relaxationmentioning

confidence: 99%

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Native and oxidized low‐density lipoproteins have different inhibitory effects on endothelium‐derived relaxing factor in the rabbit aorta

Jacobs

Plane

Bruckdorfer

1990

British J Pharmacology

184

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1 The effect of native low-density lipoproteins (LDL) and oxidized LDL (OXLDL) on the relaxations to endothelium-derived relaxing factor (EDRF) in isolated, intact aortic rings of the rabbit were investigated. 2 Native LDL induced a concentration-dependent reversible inhibition of the relaxations elicited by acetylcholine (ACh) or A23187, in rings pre-contracted by noradrenaline (NA), adrenaline (Ad) and 5-hydroxytryptamine (5-HT), but not phenylephrine (PE), which was not influenced by indomethacin. 3 The inhibition was surmountable in the rings pre-contracted with NA and Ad and only partially in those pre-contracted with 5-HT. 4 OXLDL induced an inhibition of the relaxations elicited by ACh and A23187 which was independent of the contractile agonist. The extent of inhibition and its reversibility varied with the LDL from individual donors, but was unaffected by indomethacin. 5 Native and oxidized LDL inhibited relaxations evoked by exogenous nitric oxide (NO) to the same extent. Higher concentrations of NO overcame the inhibition. The inhibition was independent of the contractile agonist and the preparation of LDL from individual donors. 6 Only OXLDL inhibited reversibly relaxations evoked by glyceryl trinitrate (GTN) and the inhibition was independent of the LDL preparation from individual donors. 7 This study demonstrates that native and OXLDL influence the response to EDRF in isolated aorta. We suggest that these lipoproteins may contribute to the attenuation of responses to EDRF found in isolated arteries from hypercholesterolaemic and atherosclerotic animals.

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Section: Introductionsupporting

confidence: 59%

Section: Preparation Of Lipoproteinsmentioning

confidence: 99%

Section: Measurement Of Endothelium-dependent Relaxationmentioning

confidence: 99%

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Native and oxidized low‐density lipoproteins have different inhibitory effects on endothelium‐derived relaxing factor in the rabbit aorta

Jacobs

Plane

Bruckdorfer

1990

British J Pharmacology

184

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“…Probucol is carried in the lipid fraction of LDL [26]. In recent studies, it has been shown that exposure to LDL inhibits the endothelium-dependent relaxation of arterial muscle in organ baths [27]. This may, in part, be explained by direct action between endothelium-derived relax-…”

mentioning

confidence: 99%

Structural changes in oxidised low‐density lipoproteins and of the effect of the anti‐atherosclerotic drug probucol observed by synchrotron X‐ray and neutron solution scattering

Bellamy

Nealis

Aitken

et al. 1989

European Journal of Biochemistry

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The atherosclerotic properties of low-density lipoproteins (LDL) are thought to be strongly enhanced by oxidation. The lipid-lowering drug probucol reduces the susceptibility of LDL to oxidation. Synchrotron X-ray and high-flux neutron solution scattering curves were used to characterise the structural properties of human LDL, before and after modification by oxidation with CuZt and the addition of probucol, in order to evaluate these techniques. Analyses based on Guinier plots, simple two-shell spherical modelling, and the use of cubic splines and indirect transformation show that a 20-h incubation with Cu2+ ions (but not 6 h) causes some of the LDL to associate to form larger aggregated particles. Gel electrophoresis on Cu2+-oxidised LDL shows a concomitant degradation of the apolipoprotein B-100 as well as the formation of high molecular mass forms. These experiments indicate that the apoprotein B-100 structure has been significantly disrupted by oxidation. The addition of probucol to LDL causes an increase in the polydispersity of LDL, as evidenced by small changes in the Guinier curves and some weakening of the minima in the X-ray scattering curves. N o changes in the quasispherical shape of LDL are observed and gel electrophoresis indicates no changes. It is possible that probucol may exert its effect by increasing the range of sizes of LDL and that the lipid-lowering effect of probucol in vivo might be caused by the preferential catabolism of the higher molecular mass forms of LDL thus created.Cardiovascular disease is implicated in half of all deaths in industrialised countries. Epidemiological studies show a strong positive correlation between elevated plasma concentrations of low-density lipoproteins (LDL) cholesterol and the risk of premature coronary heart disease [l, 21. The role of LDL is to deliver cholesterol to body tissues which require it for membrane synthesis and steroid hormone production [3]. LDL is distinguishable from all other lipoprotein classes in plasma by its high relative proportion of cholesteryl ester and the presence of a single apolipoprotein (apo) B-100. LDL has a simple quasi-spherical particle symmetry of outer diameter 21 -25 nm, as determined by electron microscopy and solution scattering [4 -81. It is composed of one molecule of apo B-100 with a 4% (by mass) oligosaccharide content (Table 1) and its binding to lipid can be likened to its insertion into a lipid vesicle [8 -121. Compositional studies show that LDL is 77% (by mass) lipid. There are about 2900 lipid molecules (Table l), primarily cholesteryl linoleate and triacylglycerol in the core, surrounded by a monolayer of polar phospholipids and cholesterol. Secondary structure predictions, circular dichroism and Fourier-transform infrared (FT-IR) spectroscopy show that apo B-100 is approximately 40% cc-helix, 25% fl-sheet and 35% random coil in its main chain conformation [9, 11, 13 - B-100 are found at the N-terminus, this part is presumed to constitute a globular structure.The presence of lipid-laden foam cells is a...

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“…12,65-68 Hypercholesterolemia, and perhaps hypertriglyThese metabolic abnormalities may also interfere ceridemia, impair endothelium-dependent relaxwith the production of NO and vasodilatory prostaation. 61,62 In diabetes there is decreased conversion glandins which inhibit mesangial cell growth and of cholesterol ester-enriched VLDL to LDL, and the matric production. 12,69 Thus, it is not surprising that resulting large and abnormal cholesterol estertreatment of hyperglycemia 70 and hypercholesteroenriched VLDL is injurious to endothelial cells follemia 67,68 favorably impact on diabetic glomerulowing receptor-mediated uptake.…”

Section: Introductionmentioning

confidence: 99%

Impact of lipid and ACE inhibitor therapy on cardiovascular disease and metabolic abnormalities in the diabetic and hypertensive patient

Sowers

1997

J Hum Hypertens

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Hypertension is often accompanied by a variety of metaabnormal more atherogenic LDL cholesterol particle. Dyslipidemia interacts with associated hemodynamic bolic abnormalities. These metabolic abnormalities include insulin resistance, dyslipidemia and abnormali-(ie, hypertension) and metabolic (ie, increased platelet aggregation and PAI-1 levels) in a multiplicative manner ties of the coagulation-fibrinolytic system predisposing to a procoagulent state. The nexus for all of these potentiating cardiovascular and renal disease. Accordingly, lipid therapy should be aggressive to attenuate abnormalities may be central (visceral) obesity. The dyslipidemia accompanying hypertension consists of low these medical complications of essential hypertension. HDL cholesterol, elevated triglyceride levels and an

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Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta

Cited by 296 publications

References 0 publications

Native and oxidized low‐density lipoproteins have different inhibitory effects on endothelium‐derived relaxing factor in the rabbit aorta

Native and oxidized low‐density lipoproteins have different inhibitory effects on endothelium‐derived relaxing factor in the rabbit aorta

Structural changes in oxidised low‐density lipoproteins and of the effect of the anti‐atherosclerotic drug probucol observed by synchrotron X‐ray and neutron solution scattering

Impact of lipid and ACE inhibitor therapy on cardiovascular disease and metabolic abnormalities in the diabetic and hypertensive patient

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