Stimulation of proliferation in stationary primary cultures of monkey aortic smooth muscle cells Part 2. Effect of varying concentrations of hyperlipemic serum and low density lipoproteins of varying dietary fat origins

Fischer-Dzoga, Katti

doi:10.1016/0021-9150(76)90144-1

Cited by 99 publications

(15 citation statements)

References 23 publications

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“…Cellular proliferation has been reported to be stimulated by LDL in combination with serum [6,7] or with growth factors [8,9] and chemically modified LDLs, such as oxLDL and acLDL, induce macrophage growth [10]. Consistently, macrophage derived foam cells, generated by uptake of modified LDL through the scavenger receptor pathway [11], tend to proliferate in atherosclerotic lesions [12,13].…”

Section: Introductionmentioning

confidence: 99%

Stimulation of mitogen activated protein kinase by LDL and oxLDL in human U‐937 macrophage‐like cells

Deigner

Claus

1996

FEBS Letters

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Mitogen activated protein kinase in extracts of U-937 macrophage-like cells was stimulated by LDL and oxLDL. A maximum value (161% of the basal phosphotransferase activity) was obtained after 6 min exposure to oxidized LDL (27 Ixg/ml) using APRTPGGRR peptide substrate. The activatory effect was more pronounced (LDL 181%, oxLDL 201%) when MAPK of stimulated cells was immnnoprecipitated with anti-p42 MArK antibodies and phuspho~ransferuse activity was assayed in immune complexes. Stimulation produced by oxLDL was inhibited by poly I, fucoidan, dextran sulfate and by the MAPKK inhibitor PD 098059 but not by PMA-mediated depletion of PKC or by pre-treatment with chioroquine or with pertussis toxin. These results suggest a direct mitogenic effect of LDL which, in the case of oxLDL, is dependent on scavenger receptor llgation but not on G-protein mediated or PKCdependent signal transduction.

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Section: Introductionmentioning

confidence: 99%

Stimulation of mitogen activated protein kinase by LDL and oxLDL in human U‐937 macrophage‐like cells

Deigner

Claus

1996

FEBS Letters

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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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“…Several possible candidates, whose blood levels can increase under various conditions in diabetes, have been considered. These include growth hormone [11][12], insulin [8,[13][14][15], cortisol [161, lipoproteins [17][18][19] and glucose [20][21][22]. In this study, the serum growth hormone levels were normal.…”

Section: Discussionmentioning

confidence: 55%

Sera from Type 2 (non-insulin-dependent) diabetic and healthy subjects contain different amounts of a very low molecular weight growth peptide for vascular cells

Koschinsky

Rütter

et al. 1985

Diabetologia

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Summary. Diabetic angiopathy may be due, in part, to increased growth in vascular cells. We have investigated serum growth factors in Type 2 (non-insulin-dependent) diabetic and healthy subjects and their effect on cultured human arterial smooth muscle cells and fibroblasts. Removal of the dialyzable serum fraction (mol. wt. < 12,000) reduced the growth effect of the diabetic sera by 37% (2p < 0.005) and of the nondiabetic sera by only 8% (2p < 0.01). In contrast, there was no difference in growth stimulation between the dialyzed diabetic or non-diabetic sera. Complete recovery of the dialyzable serum growth fraction was also obtained at a tool. wt. below 3,500. Ten times the concentration of the low molecular weight growth factor (tool. wt. <3,500) from diabetic sera stimulated growth of fibroblasts or arterial smooth muscle cells by a mean of 243% or 174% and from non-diabetic sera by a mean of 146% or 137%, respectively (2p<0.01). The growth stimulating potency of this serum fraction (mol. wt. < 3,500) contained in 10% diabetic sera, was two to ten times higher than that of human growth hormone or insulin, added in amounts equivalent to 10% or physiological serum concentrations. This diabetic serum growth factor was further characterized by: (1) linear dependence of growth stimulation over a concentration range of twenty times and by (2) reduction of the growth stimulating activity to control levels by pretreatment: (a) at 95~ for 30rain, or (b) with two different proteases: Serva pronase E (Streptomyceus griseus) or Calbiochem protease (Subtilisin calsberg). Increased amounts of the very low molecular weight serum growth peptide in Type 2 diabetes might easily penetrate the arterial wall, thus contributing to the genesis of angiopathy.Keywords: Type 2 diabetes, very low molecular weight serum growth peptide, human arterial smooth muscle cells, fibroblasts, cell culture, diabetic angiopathy.Increased vascular cell growth contributes, in part, to diabetic angiopathy. This increased growth may be under the influence of growth factors, present in sera of both diabetic and non-diabetic subjects. In Type 2 diabetic subjects, dialyzable serum growth factors (mol. wt. < 12,000) stimulate increased growth and protein synthesis in human arterial smooth muscle cells and fibroblasts [1]. The increased growth-stimulating effect of these diabetic serum factors depends on metabolic control as it tends to occur in poorly controlled but not in well controlled Type 2 diabetes [2].As the nature of these growth factors (tool. wt. < 12,000) is unknown, we have studied their effect on human mesenchymal cells in vitro in relation to (1) their specificity for diabetes, (2) their relative potency compared with growth hormone, insulin, glucagon and cortisol, and (3) their physicochemical properties, including temperature and pH stability, molecular weight and peptide nature. Table 1 shows the clinical data for the poorly controlled Type2 diabetic patients (n = 140) treated with sulphonylurea or diet alone and for the healthy subjects...

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Stimulation of proliferation in stationary primary cultures of monkey aortic smooth muscle cells Part 2. Effect of varying concentrations of hyperlipemic serum and low density lipoproteins of varying dietary fat origins

Cited by 99 publications

References 23 publications

Stimulation of mitogen activated protein kinase by LDL and oxLDL in human U‐937 macrophage‐like cells

Stimulation of mitogen activated protein kinase by LDL and oxLDL in human U‐937 macrophage‐like cells

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

Sera from Type 2 (non-insulin-dependent) diabetic and healthy subjects contain different amounts of a very low molecular weight growth peptide for vascular cells

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