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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 beta (IL-1 beta) on LDL receptor in Hep G2 cells was investigated. A greater than two-fold stimulation of the binding and internalisation of [125I]-labelled LDL at 37 degrees C was observed after an 18-h incubation of the cells with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml compared with control cells. Scatchard analysis of the binding of [125I]-labelled LDL at 4 degrees C after an 18-h incubation of the cells with 1170 units/ml IL-1 beta and 5 ng/ml TGF-beta 1 showed that they were both acting primarily by increasing LDL receptor number. The increase in LDL receptor activity could not be attributed to an increase in cell proliferation as TGF-beta 1 at concentrations from 0.05 ng/ml to 50 ng/ml had no significant effect on either cell number or [3H]thymidine incorporation into DNA whilst IL-1 beta inhibited DNA synthesis by more than 80% at a concentration of 11,700 units/ml but had significant effect on cell number. Cholesterol biosynthesis from [14C]acetate, in contrast to the stimulation of LDL receptor activity, was inhibited by approximately two-fold by incubation with TGF-beta 1 at 50 ng/ml and IL-1 beta at 11,700 units/ml.
Atherosclerosis 1992 Nov
PMID:Transforming growth factor-beta 1 and interleukin-1 beta stimulate LDL receptor activity in Hep G2 cells. 144 91

The promoter region of the endothelial cell nitric oxide synthase (ecNOS) gene contains potential response elements for transforming growth factor-beta 1 (TGF beta 1). TGF beta 1 plays an important role in the pathogenesis of atherosclerosis, vascular hypertrophy, and angiogenesis. We therefore sought to determine whether TGF beta 1 might modulate ecNOS expression in bovine aortic endothelial cells (BAEC). TGF beta 1 increased ecNOS mRNA in a dose-dependent manner. TGF beta 1 also increased ecNOS protein content. The production of nitrogen oxides (NOx), assessed by chemiluminescence, and nitric oxide synthase activity, assessed by arginine/citrulline conversion were increased in TGF beta 1-treated cells. Transcriptional activity of the 5'-flanking promoter region of the ecNOS gene was increased by TGF beta 1, as assessed by transfection with promoter/luciferase constructs. Deletion analysis suggested that the TGF beta 1-response element was present between nucleotides -1269 and -935 from the first transcription start site, in which a putative nuclear factor-1 (NF-1) binding site existed. Gel shift assays showed that nuclear protein(s), immunologically similar to CCAAT transcription factor/NF-1, bound to the putative NF-1 binding site in a sequence-specific manner. Mutation of the putative NF-1 binding site in the promoter/luciferase construct significantly decreased the responsiveness to TGF beta 1. In conclusion, TGF beta 1 increases ecNOS expression associated with an increase in production of NO in BAEC. This response is probably mediated by transcriptional activation of the ecNOS gene promoter.
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PMID:Molecular regulation of the bovine endothelial cell nitric oxide synthase by transforming growth factor-beta 1. 754

The in vivo effect of transforming growth factor-beta 1 (TGF-beta 1) was studied in a model system in which arterial intimal thickening was induced by injury of rabbit arteries with a balloon catheter (BCI). Intimal area and its ratio to medial area in carotid arteries after BCI were significantly higher in rabbits treated with 10 micrograms/kg TGF-beta 1 and 10 mg/kg aspirin i.v. QD (TGF-beta 1 group) than in those treated with 10 mg/kg aspirin i.v. QD only (control group). Intimal cell numbers in the TGF-beta 1 and control groups were not significantly different from each other, but matrix volume in the intimal layer was significantly higher in the TGF-beta 1 group. By immunohistochemical and Northern blot analyses, the fibronectin content in carotid intimal and medial layers was greater in the TGF-beta 1 group compared with that in the control group. Thus, in intimal thickenings induced by BCI. TGF-beta 1 mainly enhanced the formation of matrix containing fibronectin. Moreover, the mRNAs of TGF-beta 1 and type II receptors were detected in carotid arteries 7 and 14 days after, but not before, BCI. Thus, TGF-beta 1 influences the process of intimal thickening induced by BCI through a receptor-mediated mechanism in vivo. The significance of this fact is discussed in relation to the development of atherosclerosis.
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PMID:In vivo effect of TGF- beta 1. Enhanced intimal thickening by administration of TGF- beta 1 in rabbit arteries injured with a balloon catheter. 758 76

Previous studies in our laboratory demonstrated messenger RNA for bone morphogenetic protein-2a in human calcified plaque, suggesting that arterial calcification is a regulated process, similar to osteogenesis. To further test this hypothesis, we have isolated and cloned a subpopulation of cells from bovine aortic media that show osteoblastic potential. These novel cells are primarily distinguished from smooth muscle cells by expression of a surface marker preliminarily identified as a modified form of the ganglioside sialyl-lactosylceramide (GM3). Osteoblastic potential was indicated by high levels of alkaline phosphatase and collagen I, expression of osteopontin and osteonectin (SPARC), and production of bone-specific osteocalcin and hydroxyapatite. Cultures of these cells were stimulated to form increased numbers of calcium-mineral-producing nodules by the oxysterol 25-hydroxycholesterol as well as by transforming growth factor-beta 1, both known to be present in atherosclerotic lesions. The stimulation of calcifying vascular cells in the artery wall by these two factors suggests a possible mechanism for the colocalization of calcification with atherosclerosis in vivo.
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PMID:TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify. 818 41

The effects of platelet-derived growth factor (PDGF), transforming growth factor-beta 1 (TGF-beta 1) and interleukin-1 (IL-1) on collagen synthesis of cultured human arterial smooth muscle cells in a confluent state were investigated. Synthetic activity of collagenous protein was determined with [3H]-proline uptake, and subsequent analysis of collagen types by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by fluorography. Although PDGF (0.5 U/mL and 5.0 U/mL) enhanced total collagen synthesis per dish, it suppressed total collagen synthesis per DNA (DNA content in a dish). TGF-beta 1 (10 pmol/L and 100 pmol/L) enhanced total collagen synthesis both per dish and per DNA. IL-1 (0.1 U/mL and 1.0 U/mL) suppressed total collagen synthesis both per dish and per DNA. A fluorogram revealed that human arterial smooth muscle cells synthesize types I, III, IV and V collagen. Densitometric analysis showed PDGF suppressed the proportion of type IV collagen and increased that of type V collagen. TGF-beta 1 increased the proportions of types IV and V collagen. IL-1 elicited un- remarkable change in the proportion of collagen types. These results suggest that, in the event of human atherosclerosis, TGS-beta 1 is most effective in enhancing collagen synthesis, and PDGF modulates collagen metabolism by stimulating a cell division of smooth muscle cells with a resultant increase of collagenous protein, especially of type V collagen.
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PMID:Collagen synthesis of human arterial smooth muscle cells: effects of platelet-derived growth factor, transforming growth factor-beta 1 and interleukin-1. 849 67

We investigated the effects of lipoprotein(a) (Lp(a)) and low density lipoprotein (LDL) on proliferation of human umbilical vein endothelial cells (HUVECs). Both Lp(a) and LDL stimulated the growth of HUVECs synergistically with basic fibroblast growth factor and insulin in a dose-dependent manner. The potency of Lp(a) to promote the cell proliferation was 40% less than that of LDL. Addition of anti-transforming growth factor-beta 1 neutralizing antibody into the medium could not diminish the difference of HUVECs proliferation by Lp(a) and LDL. However, addition of anti-LDL receptor antibody suppressed HUVECs proliferation to the same level and sequestered the difference by the two lipoproteins. Moreover, cholesteryl ester content incubated with Lp(a) was 50% less than that with LDL. These results suggest that Lp(a) has less effect on HUVECs proliferation and cholesterol delivery to the cells than LDL. Therefore, Lp(a) may play a role as an atherogenic lipoprotein by delaying the repair of endothelium after injury.
Atherosclerosis 1996 Feb
PMID:Effects of lipoprotein(a) and low density lipoprotein on growth of mitogen-stimulated human umbilical vein endothelial cells. 864 76

Vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) proliferate faster and are more sensitive to transforming growth factor-beta 1 (TGF-beta 1) than those of normotensive Wistar-Kyoto rats. We studied the in vitro effects of tranilast, an anti-allergic drug, on the proliferation, migration and extracellular matrix synthesis in the SHR-VSMC. There were many inhibitory effects of tranilast (30-300 microM) on SHR-VSMC. One is the effect on the proliferation stimulated with fetal bovine serum (FBS), TGF-beta 1 and platelet-derived growth factor-BB (PDGF-BB). Another is the effect on the PDGF-BB-induced migration. Lastly, tranilast exhibited inhibitory effects on spontaneous collagen synthesis and TGF-beta 1-induced collagen and glycosaminoglycan synthesis. On the other hand, collagen induced the VSMC migration concentration-dependently. These results suggest that tranilast may prevent restenosis after percutaneous transluminal coronary angioplasty.
Atherosclerosis 1995 Dec
PMID:Inhibition of PDGF- and TGF-beta 1-induced collagen synthesis, migration and proliferation by tranilast in vascular smooth muscle cells from spontaneously hypertensive rats. 877 Mar 15

We previously reported that ascorbate (vitamin C) can regulate the growth of cultured vascular smooth muscle cells (VSMC) directly as well as by altering the properties of extracellular matrix (ECM) [Mol Cell Cardiol 1997;29:3293-303]. In the present study we compared the effects of ascorbate and transforming growth factor-beta 1 (TGF-beta1) on VSMC growth in order to determine whether their actions were mediated by similar mechanisms. When VSMC proliferation was stimulated by fetal bovine serum, the addition of TGF-beta1 (20 ng/ml) or ascorbate (1 mM) to the cell culture medium inhibited the cellular incorporation of [3H]thymidine by 19 and 59%, respectively, and by 85% when added together. The cell growth inhibitory effects of TGF-beta1 and ascorbate were partially mediated by changing the growth-regulatory properties of the ECM produced by the cells. Thus, VSMC grew more slowly on ECM deposited by VSMC under treatment with 20 ng/ml TGF-beta1 or 1 mM ascorbate (52 and 46% inhibition, respectively) than on control ECM, and their combination had an additional inhibitory effect (84%). Anti-TGF-beta1 neutralizing antibodies prevented the direct and ECM-mediated effects of TGF-beta1 on VSMC growth, but did not alter the effects of ascorbate. When ECM was pre-incubated with increasing concentrations of TGF-beta1, the growth rate of freshly plated VSMC gradually decreased, indicating that ECM-bound TGF-beta1 retained its biological activity. Comparison of the patterns of TGF-betal binding to ECM produced by VSMC in the presence or absence of ascorbate revealed no significant differences. Extraction of ECM-bound TGF-beta1 by incubation of exposed ECM with plasmin did not affect the ECM-mediated inhibitory effect of ascorbate, as the rate of proliferation of secondary VSMC cultures grown on ascorbate-dependent and independent matrices treated with plasmin were equally increased. These results suggest that the amount of ECM-bound TGF-beta1 was not altered by ascorbate. The secretion of TGF-beta1 into the cell culture medium by VSMC also did not depend on the ascorbate supply. Finally, addition of heparin to the VSMC culture medium during ECM production abolished the ECM-mediated growth inhibitory effects of ascorbate, but did not affect the action of TGF-beta1. Our data demonstrate that the growth inhibitory effects of ascorbate on cultured VSMC are independent of the action of TGF-beta1, and the effects of these two compounds on VSMC growth are additive.
Atherosclerosis 1998 Sep
PMID:Transforming growth factor-beta 1 and ascorbate regulate proliferation of cultured smooth muscle cells by independent mechanisms. 973 12

Oxidized low-density lipoprotein (OxLDL) has been implicated in atherosclerosis and glomerulosclerosis. LOX-1 is a recently identified OxLDL receptor that is abundantly expressed in vascular endothelial cells. The aim of the present study was to investigate LOX-1 expression in the kidneys of hypertensive rats. Dahl salt-sensitive (DS) and salt-resistant (DR) rats were fed a 0.3% or 8% NaCl diet. Some DS 8% rats were treated with manidipine or hydralazine. LOX-1 gene expression was markedly elevated in the kidneys and glomeruli of hypertensive DS 8% rats compared with those of normotensive DR and DS 0.3% rats. Prolonged salt loading further increased the renal LOX-1 expression in DS rats. The LOX-1 upregulation in DS 8% rats was accompanied by renal overexpression of transforming growth factor-beta 1 and type I collagen, impaired renal function, and histologic glomerulosclerotic changes, all of which were ameliorated by antihypertensive treatment. LOX-1 was indeed expressed in the glomeruli in vivo and in cultured glomerular cells in vitro. However, LOX-1 expression was elevated in the aorta but not the kidneys of spontaneously hypertensive rats, which exhibited hypertension but minor glomerulosclerotic changes. In conclusion, the LOX-1 upregulation in the kidney of DS 8% rats was parallel to glomerulosclerotic changes and renal dysfunction, suggesting a possible pathogenetic role for renal LOX-1 in the progression to hypertensive glomerulosclerosis.
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PMID:Expression of LOX-1, an oxidized low-density lipoprotein receptor, in experimental hypertensive glomerulosclerosis. 1100 13

Atherosclerotic vascular disease is a major cause of death for uremic patients who are on hemodialysis (HD). Recent evidence suggests that lipoprotein (a) [Lp(a)] may aggravate atherosclerosis by inhibiting activation of transforming growth factor-beta 1 (TGF-beta 1). Plasma Lp(a) and plasma TGF-beta 1 activation in HD patients (n = 51), chronic renal failure patients not subjected to hemodialysis (non-HD-CRF; n = 12), and healthy volunteers (control; n = 13) were investigated. Plasma Lp(a) was significantly higher in HD (18.75 +/- 1.62 mg/ml) and non-HD-CRF patients (25.0 +/- 8.4 mg/ml) than in control subjects (10.9 +/- 5.8 mg/ml). The degree of atherosclerosis in HD patients was assessed by measuring the intima-media thickness (IMT) and plaque score with the use of an ultrasound scanner. IMT and plaque score were higher in HD and non-HD-CRF patients than in controls. A significant positive correlation was found in HD patients between Lp(a) and IMT (r = 0. 377, P < 0.01) as well as between Lp(a) and plaque score (r = 0.43, P < 0.01). Plasma total TGF-beta 1 significantly increased in HD (119.8 +/- 53.5 ng/ml) and non-HD-CRF patients (93.2 +/- 25.0 ng/ml) compared with control subjects (17.7 +/- 6.4 ng/ml), whereas the plasma level of mature (active) TGF-beta1 did not differ among the groups. When plasma TGF-beta 1 and supernatant TGF-beta 1 from cultured peripheral mononuclear cells were compared before and after an HD session, neither total nor mature TGF-beta 1 showed a significant difference between the values before and after an HD session. There were no significant relationships between plasma total TGF-beta 1 and IMT or plaque score, between mature TGF-beta 1 and IMT or plaque score, or between mature TGF-beta 1 and Lp(a). In conclusion, Lp(a) may be an important atherogenic factor in CRF patients. However, it was not clarified whether Lp(a) exerts its effect by inhibiting TGF-beta 1 activation in CRF patients.
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PMID:Role of lipoprotein (a) and TGF-beta 1 in atherosclerosis of hemodialysis patients. 1100 20


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