The participation of aortic proteins in the formation of complexes between low density lipoproteins and intima-media extracts

Camejo, G; Lopez, Amado; Vegas, Héctor; Paoli, Hugo

doi:10.1016/0021-9150(75)90095-7

Cited by 51 publications

(9 citation statements)

References 14 publications

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“…23 -26 It has not yet been established how much of the additionally extractable apoB is complexed to aortic tissue or how much represents lipoproteins physically trapped within the homogenate. There are a number of reports in the literature concerning the binding of lipoproteins to arterial elastin, 31 -32 glycoproteins, 33 and collagen. 34 - 35 The precise interaction of VLDL and LDL with substances in the lipid core of a plaque remains to be identified.…”

Section: Discussionmentioning

confidence: 98%

Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta.

Hoff

Heideman

Gotto³

et al. 1977

Circulation Research

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Apoliporotein B (apoB) was measured in buffer-extracted homogenates of grossly normal and artherosclerotic human aortic intima by means of an electroimmunoassay procedure. The apoB values which were expressed as microgram per mg tissue dry weight, varied widely, ranging from 0.34 to 18.45 in normal intima and from 0.8 to 12.5 in fatty fibrous plaques. No consistent differences in apoB content were found between normal intimas from thoracic and abdominal aortic regions. There was a statistically significant positive correlation between the quantity of buffer-extractable apoB in normal regions and the plasma cholesterol and triglyceride concentration. Buffer-extractable apoB values were significantly higher in fatty fibrous plaques than in ulcerated lesions from the same vessel. However, fatty fibrous plaque apoB values were significantly lower than those from grossly normal regions from the same aorta, although the topographical distribution of apoB was more widespread in plaques than in normal regions, as shown by immunofluorescence studies. This apparent discrepancy reflected the incomplete extraction of apoB from plaques as contrasted to normal regions. The relatively loosely bound apoB, extractable by standard buffers, may represent intact low density lipoprotein (LDL) and/or very low density lipoprotein (VLDL), while the tightly bound fraction may represent insoluble complexes of intact lipoproteins within the plaque or delipidated apoB.

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Section: Discussionmentioning

confidence: 98%

Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta.

Hoff

Heideman

Gotto³

et al. 1977

Circulation Research

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“…The key events in the initiation of ASCVD are the retention and accumulation of cholesterol-rich apoB-containing lipoproteins within the arterial intima at sites of predilection for plaque formation. 5–9 Notably, LDL and other apoB-containing lipoproteins <70 nm in diameter (including VLDL, their remnants, IDL, and Lp(a)) efficiently enter and exit the arterial intima. 9 , 10 At what is now considered physiologically relevant levels of LDL cholesterol [LDL-C; ∼0.5–1.0 mmol/L (20–40 mg/dL), typical of newborns 11 and a wide range of mammalian species 12 ], the probability of LDL particle retention and the risk of developing atherosclerosis is low.…”

Section: Pathophysiology Of Atherosclerosismentioning

confidence: 99%

“…Plausibility 1 LDL and other apolipoprotein (apo) B-containing lipoproteins (very low-density lipoprotein their remnants, intermediate-density lipoprotein and lipoprotein(a)) are directly implicated in the initiation and progression of ASCVD; experimentally induced elevations in plasma LDL and other apoB-containing lipoproteins lead to atherosclerosis in all mammalian species studied. 2 , 5–12 2. Strength 1 Monogenic and polygenic-mediated lifelong elevations in LDL lead to markedly higher lifetime risk.…”

Section: Introductionmentioning

confidence: 99%

Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

Ference

Ginsberg

Graham

et al. 2017

European Heart Journal

2,776

1,653

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AimsTo appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).Methods and resultsWe assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150 000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects.ConclusionConsistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.

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“…78 Such binding substances are apparently not present in the adventitia of arteries and are absent from veins. 79 Consequently, the presence of such binding factors in arteries may predispose them to lipid accumulation. 80 ' 81 By 3 to 4 months of hypercholesterolemia, fatty streaks are macroscopically visible and, as observed in humans, are preferentially found in proximity to branches and bifurcations.…”

Section: Fatty Streak Formation and Progressionmentioning

confidence: 99%

Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation.

Faggiotto¹,

Ross²,

Harker³

1984

Arteriosclerosis

900

297

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Morphologic studies resulting from events that occur during the development of the lesions of atherosclerosis were studied In chronic, diet-induced hypercholesterolemia In a series of nonhuman primates. Within 12 days of hypercholesterolemia In Macaca nemestrina, monocytes became adherent to the surface of the endothelium. These monocytes appeared to migrate subendothelially, accumulate lipid, and become lipld-laden macrophages (foam cells). Within a month, a "seroflbrinous insudate" formed together with variable numbers of subendothellal llpid-laden macrophages. By the second month, foam cells increased In number, often in multilayers, to form a fatty streak. Concomitantly, the luminal surface of the arteries became increasingly Irregular due to the subendothelial accumulation of foam cells. Numerous monocytes continued to attach to the endothelial surface over the fatty streaks, and many of them appeared to enter the Intlma and participate In the growth of the fatty streaks. Lipid-laden smooth muscle cells appeared in small numbers and formed two to four layers between the macrophages and the internal elastic lamella at 2 to 3 months. During the third month of hypercholesterolemla, endothelial cell continuity over the llpid-laden macrophages became Interrupted, exposing the underlying foam cells to circulating blood. Foam cells were then readily observed In whole blood smears, suggesting that many of the lipld-laden macrophages leave the intima and enter the circulation.After 4 months, significant endothelial denudation was found In the lilac artery and many exposed macrophages were covered by adherent platelets in the form of a mural thrombus. Thus, the early components of atherosclerosis induced by chronic hypercholesterolemla centered around the monocyte-macrophage and its interaction with endothelium In the induction of the fatty streak. Subsequent changes that lead to macrophage-smooth muscle Interactions, platelet-macrophage Interactions, and platelet-endothelial interactions appeared to set the stage for the development of more advanced proliferatlve lesions. (Arteriosclerosis 4:323-340, July/August 1984)

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The participation of aortic proteins in the formation of complexes between low density lipoproteins and intima-media extracts

Cited by 51 publications

References 14 publications

Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta.

Apolipoprotein B retention in the grossly normal and atherosclerotic human aorta.

Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel

Studies of hypercholesterolemia in the nonhuman primate. I. Changes that lead to fatty streak formation.

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