Effects of Serum Lipoproteins on the Morphology, Growth, and Metabolism of Arterial Smooth Muscle Cells

Fisher-Dzoga, Katti; Chen, Robert; Wissler, Robert W.

doi:10.1007/978-1-4684-3243-5_15

Cited by 55 publications

(8 citation statements)

References 6 publications

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“…This increased to upward of 10-15 ^.g of cholesterol/mg of protein as cholesteryl ester with addition of LDL or hypercholesterolemic serum to the culture medium. A similar increase in cellular cholesteryl ester content has been described in skin fibroblasts 25 and in smooth muscle cells grown from primary explants of rabbit aorta 26 as well as in organ cultures of pigeon aorta. 6 Thus, the response to LDL in both a stimulation of cholesterol esterification as well as accumulation of cholesteryl esters is not just a peculiarity of cells in culture.…”

Section: Discussionsupporting

confidence: 77%

Stimulation of cholesterol esterification in rhesus monkey arterial smooth muscle cells.

Clair¹,

Smith²,

Wood³

1977

Circulation Research

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SUMMARY The influence of homologous high density lipoprotein (HDL) and low density lipoprotein (LDL) and of whole hypercholesterolemic serum on the esterification of oleic acid and cholesterol was studied in rhesus monkey arterial smooth muscle cells. Whole hypercholesterolemic serum and isolated LDL stimulated cholesterol esterification as much as 10-fold using either cholesterol-1,2-3 H or oleate-l-14 C as substrate. At the same concentrations of cholesterol, HDL stimulated cholesterol esterification to a lesser extent, to a maximum of 3-fold. Associated with the stimulation of cholesterol esterification by LDL or whole hypercholesterolemic serum was a greater than 10-fold increase in the cholesteryl ester content of the arterial smooth muscle cells.Esterification to cholesterol reached a maximum after 8-12 hours of culture with either hypercholesterolemic serum or LDL. The stimulation of esterification was specific for esterification to cholesterol because there was little change in incorporation of fatty acid into triglycerides and phospholipids. These studies provide further evidence that a major consequence of the interaction of plasma LDL with the cellular elements of the arterial wall is a stimulation of cholesterol esterification. These studies, coupled with the observation that cholesteryl esters, more than any other single component, increase in the atherosclerotic artery, suggest an important role of a stimulation in cholesterol esterification in the pathogenesis of atherosclerosis.THERE NOW IS considerable information available describing the metabolic changes that occur in atherosclerotic arterial tissue.1 These include a number of alterations in the metabolism of proteins, carbohydrates, and lipids within the atherosclerotic artery. Although all of these metabolic changes contribute to the final expression of the disease, it is difficult to know which of them play a primary role in the initiation of the atherosclerotic lesion and which are results of the disease.The fact that cholesteryl esters accumulate within the atherosclerotic artery has been recognized for some time. 2As has been shown, an increase in arterial cholesteryl ester content is one of the first changes to occur in the arterial wall in experimentally produced atherosclerosis. This suggests that an alteration of cholesteryl ester metabolism may play a role in the initial events in the pathogenesis of atherosclerosis.3 Consistent with this hypothesis is the fact that a stimulation of cholesterol esterification can be demonstrated in arterial tissue prior to the appearance of grossly visible atherosclerotic lesions. Although cholesterol esterification appears to be one of the first metabolic parameters altered in the development of the atherosclerotic lesion, the actual mechanism of this stimulation is unclear. Considerable evidence suggests that it may result from the interaction of circulating plasma lipoproteins with the cellular elements of the arterial wall.3 "' To study the influence of a single component, such

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Section: Discussionsupporting

confidence: 77%

Stimulation of cholesterol esterification in rhesus monkey arterial smooth muscle cells.

Clair¹,

Smith²,

Wood³

1977

Circulation Research

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“…They do not contract in response to angiotensin II or norepinephrine or to electrical or mechanical stimulation (7,17,18) but readily synthesize collagen, elastin, and glycosaminoglycans (1,2,16,22,23,32) and are thus in a synthetic state . Subcultured aortic smooth muscle cells exposed to the platelet-derived growth factor (PDGF) in whole blood serum (WBS) proliferate in a dose-dependent manner with cell division commencing within 24 to 36 h of challenge (25)(26)(27)(28), and smooth muscle which has migrated from aortic explants, proliferated, and reached a stationary growth phase can be stimulated to another proliferative phase by increased amounts of PDGF, hyperlipemic serum, or its low-density lipoprotein (LDL) within 1-2 d of challenge (8)(9)(10)(11)) .…”

mentioning

confidence: 99%

Phenotype-dependent response of cultured aortic smooth muscle to serum mitogens.

Chamley-Campbell¹,

Campbell²,

Ross³

1981

The Journal of Cell Biology

426

158

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Smooth muscle cells from the aortic media of adult pigs and monkeys have been grown in primary culture by plating cells enzymatically dissociated from the intact aorta. During the first 6 d these cells are in the "contractile" phenotype. That is, they contract slowly in response to angiotensin II and their cytoplasm is filled with both thick and thin myofilaments . In this state they do not incorporate [3H]thymidine into DNA or proliferate in response to normolipemic or hyperlipemic whole blood serum (WBS) . After 7 d in culture the cells undergo a spontaneous modulation of phenotype to a "synthetic" state where they cannot be stimulated to contract and their cytoplasm is filled with organelles usually associated with synthesis of secretory protein . Thick myosin-containing filaments can no longer be demonstrated . When challenged with normolipemic or hyperlipemic WBS the cells incorporate [3H]thymidine into DNA and undergo logarithmic growth . It is suggested that when smooth muscle is in the contractile phenotype (as normally exists for most cells in the aortic media of adult animals) it does not divide when challenged with serum mitogens but can undergo a change of phenotype to a synthetic state in which division can be stimulated .Differentiation of a cell involves transition from an initially multipotential state to the specialized form typical of the adult . A fully differentiated cell is one therefore that has lost all potentiality to develop into another cell type . The concept of cell modulation encompasses the fact that a fully differentiated cell can assume a different function (with associated morphological changes) in response to an altered environment without any change in its type-specific character. Modulation is therefore reversible.The smooth muscle cell is the only cell type present in the media of mammalian arteries (19). It must therefore be responsible not only for maintaining artery wall tension via contraction-relaxation but also for vascular remodeling, repair, and growth . These latter functions require the retention in the adult of certain basic mesenchymal properties, namely the abilities to synthesize extracellular matrix and to divide (33). This multiplicity of functions requires a whole spectrum of variation in morphology or phenotype. At one end of the spectrum is the smooth muscle cell whose major function is contraction . The cytoplasm of this cell is largely filled with thick and thin myofilaments and it has been described as being in the "contractile" state (6) . The vast majority of cells in the media of the adult aorta are in this phenotype. At the other end of the spectrum is the smooth muscle cell engaged in the synthesis of extracellular matrix and/or division. The cytoplasm of this cell

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“…Supporting the hypothesis are in vitro observations indicating that lipoprotein, especially low density lipoprotein, as well as a platelet factor will lead to increased proliferation of vascular smooth muscle cells (15)(16)(17). In addition, increased concentration of low density lipoprotein will lead to lipid accumulation within these cultured cells.…”

mentioning

confidence: 76%

Effect of regenerated endothelium on lipid accumulation in the arterial wall.

Minick¹,

Stemerman²,

Insull³

1977

Proc. Natl. Acad. Sci. U.S.A.

102

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We tested the hypothesis that loss of endothelium results in increased transport of lipoprotein into the arterial wall, favors accumulation of lipid, and thus predisposes to atherosclerosis. In rabbits initially fed a diet low in lipid, the aortas were de-endothelialized with an intraarterial balloon catheter; 28 days later, the animals were divided into two groups. Group I animals were continued on a diet low in lipid and sacrificed at 8, II, 13, and 15 weeks after de-endothelialization. Group II animals were fed the same diet supplemented with 0.5% cholesterol and sacrificed at comparable intervals.Aortas of group I animals revealed proliferative fibromuscular intimal thickening in both de-endothelialized and re-endcothelialized areas, with little or no fatty change in the intima.

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Effects of Serum Lipoproteins on the Morphology, Growth, and Metabolism of Arterial Smooth Muscle Cells

Cited by 55 publications

References 6 publications

Stimulation of cholesterol esterification in rhesus monkey arterial smooth muscle cells.

Stimulation of cholesterol esterification in rhesus monkey arterial smooth muscle cells.

Phenotype-dependent response of cultured aortic smooth muscle to serum mitogens.

Effect of regenerated endothelium on lipid accumulation in the arterial wall.

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