Influx in vivo of low density, intermediate density, and very low density lipoproteins into aortic intimas of genetically hyperlipidemic rabbits. Roles of plasma concentrations, extent of aortic lesion, and lipoprotein particle size as determinants.

Nordestgaard, B. G.; Tybjærg‐Hansen, Anne; Lewis, Barry

doi:10.1161/01.atv.12.1.6

Cited by 129 publications

(79 citation statements)

References 42 publications

(34 reference statements)

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“…This idea is supported by the finding that the majority of the cholesterol entering the vessel wall is a component of the apoB-containing lipoproteins, such as the LDL. 30 Thus, differences in HDL levels probably did not cause any discrepancy in cholesterol entry into the vessel wall. Clearly, more detailed studies are needed to elucidate the mechanism behind the selective accumulation of free cholesterol when apoA1 is absent.…”

Section: Discussionmentioning

confidence: 96%

ApoA1 Reduces Free Cholesterol Accumulation in Atherosclerotic Lesions of ApoE–Deficient Mice Transplanted With ApoE–Expressing Macrophages

Boisvert

Black

Curtiss

1999

ATVB

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Abstract-Along with apolipoprotein (apo) E, which promotes cholesterol efflux from foam cells, apoA1-containing high density lipoprotein (HDL) is thought to facilitate the transport of cholesterol from lesions. This role for apoA1 was tested in vivo by lethally irradiating apoE-deficient and apoE-plus apoA1-deficient mice and reconstituting them with bone marrow cells isolated from wild-type (WT) mice. ApoE, but not apoA1, was synthesized by the transplanted bone marrow-derived cells. Therefore, this transplantation procedure generated apoE-deficient animals with atherosclerotic lesions that contained both apoE and apoA1 (E/A1 mice) and apoE-deficient animals with lesions that contained apoE but no apoA1 (E/A1o mice). As shown previously, the transplanted WT macrophage-derived apoE dramatically lowered the plasma hypercholesterolemia in both groups. On feeding with an atherogenic diet after transplantation, plasma cholesterol levels were raised in both groups of mice, but the levels in the E/A1 mice at 20 weeks were 2-to 3-fold higher than in E/A1o mice. Immunohistochemical staining verified that apoE was abundant in lesions of both groups, whereas apoA1 was detected in the lesions of E/A1 mice only. Despite a 2-to 3-fold lower total plasma cholesterol in the E/A1o mice, the free cholesterol recovered from isolated aortas was Ϸ60% higher and the mean lesion area in serial sections of the aortic valves 45% larger.

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Section: Discussionmentioning

confidence: 96%

ApoA1 Reduces Free Cholesterol Accumulation in Atherosclerotic Lesions of ApoE–Deficient Mice Transplanted With ApoE–Expressing Macrophages

Boisvert

Black

Curtiss

1999

ATVB

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“…2 " 7 ' 46 ' 47 In a case-control study, 5 the relative amount of chylomicron remnants in lipoproteins S f >60 was a significant predictor of coronary artery disease. Notably, in the present study, this fraction was significantly reduced by gemfibrozil.…”

Section: Discussionmentioning

confidence: 99%

Gemfibrozil reduces postprandial lipemia in non-insulin-dependent diabetes mellitus.

Syvänne

Vuorinen-Markkola

Hilden

et al. 1993

Arterioscler Thromb

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The effect of gemfibrozil on postprandial lipoprotein metabolism was investigated in a 12-week, randomized, double-blind, placebo-controlled trial in 20 non-insulin-dependent diabetic patients with moderate hypertrigryceridemia. The patients were given a meal containing 78 g of fat and 345,000 units of vitamin A to label chylomicrons and their remnants. Plasma obtained at various times during the fat-load test was separated into six fractions by gradient-density ultracentrifugation. Gemfibrozil reduced the postprandial triglyceride response, measured as the area under the time-dependent concentration curve, on average by 32% in whole plasma, by 38% in the Svedberg flotation unit (S f ) 1,100-3,200 chylomicron fraction, by 36% in S, 400-1,100 chylomicrons, and by 38% in the S, 60-400 lipoproteins. Retinyl palmitate, a measure of intestinally derived particles, was reduced in plasma by 34%, in S r 1,100-3,200 by 46%, in S, 400-1,100 by 44%, and in S, 60-400 by 37%. All these reductions were significant in comparison with the placebo group. Particles with S r <60 were not significantly affected. In contrast to earlier observations in healthy subjects, no significant negative correlations existed between postprandial lipemia and high density lipoprotein cholesterol or the postheparin lipoprotein lipase activity. The reduction of the potentially atherogenic chylomicron remnants may decrease the risk of atherosclerosis in non-insulin-dependent diabetes mellitus, a hypothesis that awaits testing in prospective studies. 4 Moreover, recent case-control studies 5 -7 have suggested that individuals with angiographically verified coronary artery disease have elevated levels of chylomicron remnants in their postprandial plasma compared with control subjects without coronary lesions. (Arteriosclerosis and Thrombosis 1993;13:286-295) KEY WORDS • non-insulin-dependent diabetes mellitus • chylomicrons • triglyceride-rich lipoproteins • chylomicron remnants • postprandial lipemia • lipid-lowering therapy • fibrates • gemfibrozilThe risk of atherosclerotic vascular disease is markedly increased in non-insulin-dependent diabetes mellitus (NEDDM). Most of this excess morbidity cannot be explained by the conventional risk factors. 8 In general, NIDDM patients have increased fasting levels of TRLs, From the First (M.S.), Second (H.V.-M.), and Third

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“…I suggest that multiple aspects of their lipid profiles are atherogenic. First, not only are there increased levels of VLDL particles, which can enter the vessel wall and accumulate in atherosclerotic plaques (27,28), but these VLDL are, by virtue of receiving CETP-transferred cholesteryl esters, able to deliver more cholesterol per particle to the vessel wall. Additionally, increased VLDL secretion can contribute to postprandial hyperlipidemia by providing competition for chylomicron clearance pathways; postprandial hyperlipidemia is independently associated with CAD (29).…”

Section: Perspective Seriesmentioning

confidence: 99%

Insulin resistance and cardiovascular disease

2000

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Influx in vivo of low density, intermediate density, and very low density lipoproteins into aortic intimas of genetically hyperlipidemic rabbits. Roles of plasma concentrations, extent of aortic lesion, and lipoprotein particle size as determinants.

Cited by 129 publications

References 42 publications

ApoA1 Reduces Free Cholesterol Accumulation in Atherosclerotic Lesions of ApoE–Deficient Mice Transplanted With ApoE–Expressing Macrophages

ApoA1 Reduces Free Cholesterol Accumulation in Atherosclerotic Lesions of ApoE–Deficient Mice Transplanted With ApoE–Expressing Macrophages

Gemfibrozil reduces postprandial lipemia in non-insulin-dependent diabetes mellitus.

Insulin resistance and cardiovascular disease

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