Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular smooth muscle cell proliferation is regarded as a key early event in the pathogenesis of atherosclerosis. Heparin-binding growth factor (HBGF)-1 and HBGF-2, also referred to as acidic and basic fibroblast growth factor, are potent mitogens for human vascular smooth muscle cells. These cells coexpress HBGF-1 and HBGF-2 and thus represent a vessel wall source for both polypeptides. In this report, we demonstrate that HBGF-1 and HBGF-2 expression is increased when quiescent human smooth muscle cells are treated with fetal bovine serum. The kinetics of HBGF-1 and HBGF-2 mRNA accumulation following serum treatment are distinct. In addition, HBGF-1 transcripts remain elevated for a longer time period; this may reflect the different decay rates of the HBGF-1 and HBGF-2 mRNAs. Serum-inducible HBGF-1 and HBGF-2 mRNA expression does not occur when RNA synthesis is repressed by actinomycin D but can occur in the presence of cycloheximide, an inhibitor of protein synthesis. Immunoprecipitation experiments indicate that serum treatment also increases HBGF-1 and HBGF-2 production. Smooth muscle cells treated with phorbol 12-myristate 13-acetate or certain combinations of polypeptide growth factors also express increased levels of HBGF-1 and HBGF-2 transcripts. Potential sources for these growth factors in vivo include platelets, macrophages, and T lymphocytes; thus, smooth muscle cells located at sites of vascular injury or inflammation may express elevated levels of HBGF-1 and HBGF-2.
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PMID:Serum, phorbol ester, and polypeptide mitogens increase class 1 and 2 heparin-binding (acidic and basic fibroblast) growth factor gene expression in human vascular smooth muscle cells. 172 53

Numerous studies have shown that early radiation injury is characterized by vascular damage and that the initial site of damage appears to be the EC lining of the vessel wall. Chronic irreversible tissue reactions to radiation include thrombotic occlusion of capillaries, enhanced atherosclerosis in larger vessels, inflammatory changes, and late tissue fibrosis. These processes may be mediated by endothelial products released as a result of cellular injury. Using EC cultures, we show that ionizing irradiation affects one of the major vascular defense mechanisms against platelet activation, thrombosis, and atherosclerosis--the capacity to produce PGI2. Dose- and time-related damage to enzymes of the arachidonic acid cascade were demonstrated. Radiation damage is associated with oxidant stress and production of free radicals. The oxygen radical scavenger, vitamin C, was found to protect the capacity of irradiated ECs to produce PGI2. Radiation injury often induces an acute inflammatory response. We found that irradiated ECs release a chemotactic factor for neutrophils, which is a lipid product of the lipoxygenase pathway. Late radiation-induced tissue fibrosis and the capacity of radiation to enhance arteriosclerosis may involve participation of mitogens released from perturbed and damaged ECs. We show that conditioned medium of irradiated ECs contain larger amounts of newly synthesized mitogens capable of stimulating the proliferation of fibroblasts, SMCs, and ECs. Hence, it may be assumed that the mitogenic activity released by irradiated ECs includes both PDGF and FGF-like mitogens.
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PMID:Perturbation of endothelial functions by ionizing irradiation: effects on prostaglandins, chemoattractants and mitogens. 266 90

T cell infiltration is prevalent in wound healing, atherosclerosis, vascular lesions in chronic allograft rejection, and autoimmune diseases. Whether T cells play a role in the migration and proliferation of vascular smooth muscle cells and endothelial cells in these lesions is not known. We previously reported that some human T cells express FGF-1, a potent growth factor for vascular smooth muscle cells and endothelial cells. In this study, we extend this observation and examine the expression and function of FGF receptors on human T cells. Using reverse transcription-PCR, Northern analysis, and immunohistochemistry, we found that some human T cells also express high affinity FGF receptor 1 (FGFR-1) respond to FGF-1. In the presence of anti-CD3, exogenous FGF-1 functions as a costimulator for these T cells, while FGF-1 alone does not induce T cell proliferation. [3H]Thymidine incorporation is sevenfold higher in T cells costimulated with FGF-1 compared with stimulation with anti-CD3 alone. Using limiting dilution, we demonstrate that FGF-responsive T cells are present in normal peripheral blood at a mean frequency of 1:19780 (95% confidence limits, 1:15100-1:23000), and similar T cells are increased in the peripheral blood of heart transplant recipients (mean frequency, 1:4210; 95% confidence limits, 1:3420-1:6781). In addition, a subline of Jurkat, a human T cell tumor, expresses FGFR-1 receptor. The function of FGFR-1 receptor in Jurkat T cells is demonstrated by the production of IL-2 after stimulation with FGF-1 and anti-CD3. IL-2 levels are sevenfold higher in Jurkat T cells costimulated with FGF-1 compared with those stimulated with anti-CD3 alone. FGF-1 alone has no effect on Jurkat T cells. These findings thus provide evidence that a subset of human T cells expresses a receptor for vascular cell growth factors, and this receptor functions to increase IL-2 production consistent with costimulation. The potential role of FGF-responsive T cells in a variety of vascular and inflammatory lesions is discussed.
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PMID:Costimulation of human CD4+ T cells by fibroblast growth factor-1 (acidic fibroblast growth factor). 756 Oct 97

Basic fibroblast growth factor (bFGF) exerts a differential effect on DNA synthesis, bFGF mRNA synthesis, and expression of FGF-receptor genes by cultured smooth muscle cells from aortae of newborn and adult rats (used as a model in atherosclerosis research). Cells from adult animals, are more sensitive to bFGF, and bFGF triggers its own mRNA synthesis. Moreover, the level of the transcript of the FGFR-1 gene (coding for the most abundant FGF-receptor in smooth muscle cells) is higher in smooth muscle cells from adult rats. In contrast, the FGFR-3 gene only is expressed in smooth muscle cells from newborn rats. Crosslinking of [125I]bFGF to its receptor showed 130 kDa and 160 kDa complexes both in newborn and adult smooth muscle cells.
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PMID:Expression of basic fibroblast growth factor and fibroblast growth factor receptor genes in cultured rat aortic smooth muscle cells. 771 Oct 64

Based upon literature the renin-angiotensin system involvement in the pathogenesis of atherosclerosis has been discussed. Angiotensin II leads to the increased production of growth factors such as PDGF, TGF-beta, FGF and extracellular matrix proteins. There are evidences that angiotensin II stimulates expression of egr-1, c-jun, c-fos and c-myc oncogenes in vascular smooth muscle cells. Proliferation of aortic smooth muscle cells in response to the injury can be reduced by inhibitors of renin-angiotensin system what supports the hypothesis that angiotensin II can contribute to the pathogenesis of atherosclerosis.
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PMID:[Renin-angiotensin system and atherosclerosis]. 820 30

Previous studies of age-related susceptibility to viral infection have focused largely on the effects of aging on the immune response. Little attention has been given to age-related changes in the infectivity of target cells. We show here a fourfold greater plating efficiency of herpes simplex virus type 1 (HSV-1) for cultured vascular smooth muscle cells derived from adult rats compared with cells from genetically identical pup rats. The difference in plating efficiency appeared to be due to differences in initial attachment of the virion to the cell surface. There were no differences in the rate of viral entry or the efficiency of viral replication at high multiplicities of infection and no resistant "subpopulation" of pup cells. The pup cells did not release a soluble inhibitor of infection. Infection in both cell types was inhibited similarly by basic fibroblast growth factor (bFGF). Although adult cells exhibited a more vigorous mitogenic response to bFGF than did pup cells, binding studies did not demonstrate significant differences in the binding of bFGF to the cell surface, suggesting that differential expression of high-affinity FGF receptors could not be correlated with the difference in infectivity. We speculate that differences in the distribution of heparan sulfate in the cell surface, which serves as the initial attachment site for HSV-1, may explain the observed differences in plating efficiency. Since age is a risk factor for the development of atherosclerosis, these results have potential implications for susceptibility of the vasculature to herpesviral infections as a function of the development of the vessel wall.
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PMID:Developmentally regulated herpesvirus plaque formation in arterial smooth muscle cells. 838 74

Basic fibroblast growth factor (bFGF) is a potent smooth muscle cell mitogen. Smooth muscle cell and macrophage-derived foam cells, resulting from cholesteryl ester accretion, are hallmark characteristics of atherosclerosis. We wanted to determine if bFGF synthesis is altered during cholesteryl ester accumulation in smooth muscle cells. Cholesteryl ester enrichment causes a 3-fold increase in bFGF in cellular lysates and a 3-fold increase in steady state mRNA levels for bFGF, as compared with control cells. Conditioned media from cholesteryl ester-enriched smooth muscle cells contains 6 times more mitogenic activity than conditioned media from control cells; this activity is neutralized by an antibody directed against bFGF but not by an antibody directed against platelet-derived growth factor. These results suggest that cholesteryl ester enrichment also enhances bFGF release. Since oxysterols have been implicated in the pathogenesis of atherosclerosis, we determined if oxysterols could affect bFGF production and release. 25-Hydroxycholesterol also increases the release of bFGF-like mitogens from smooth muscle cells, as well as increasing mRNA transcript levels for bFGF. Cholesteryl ester enrichment and 25-hydroxycholesterol did not promote bFGF release secondary to cell injury. In conclusion, these data define a basic mechanism for smooth muscle cell hyperplasia during atherogenesis involving the generation of bFGF by smooth muscle cell-derived foam cells.
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PMID:Induction of basic fibroblast growth factor mRNA and protein synthesis in smooth muscle cells by cholesteryl ester enrichment and 25-hydroxycholesterol. 846 21

The reactivity and the structure as well as the growth of the vascular wall depend on a variety of locally synthetised factors in a process of a permanent structure-function adaptation. These substances exert their inhibitory or stimulatory growth effects by paracrine or autocrine mechanisms. These factors command the reorganisation of the structure of existing blood vessel or the creation of new vessels. They are synthetised and secreted form either endothelial and smooth muscle cells or circulating cells (in particular macrophages, platelets). The growth factors are multiple and interactive insuring a role of physiological vascular modeling in normal conditions but they may participate and even induce dramatic structural dysfunctions that are observed in pathologies such as venous diseases, atherosclerosis or hypertension. Among them, the polypeptides PDGF (platelet derived growth factor), FGF (fibroblast growth factor) and TGF beta (transforming growth factor beta) play a major role. Other factors like cytokines, IGFs (insulin like growth factors), PAF (platelet activating factor) endothelins or nitric oxide have also to be considered. Thus, the vascular wall structure is under the influence of a complex group of growth factors which become to be identified and may be the targets of new therapies of the vessels.
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PMID:Growth factors and vascular wall. 880 32

Fibroblast growth factor 1 (FGF-1 or aFGF), is a mitogen for a variety of mesoderm- and neuroectoderm-derived cells, as well as an angiogenic factor in vivo. It has been implicated in angiogenic diseases including atherosclerosis, cancer and inflammatory autoimmune diseases. As part of an effort to understand the role of FGF-1 in the pathobiology of inflammation, we have isolated and characterized the mouse Fgf-1 gene. Southern blot analysis of mouse genomic DNA using the mouse Fgf-1 cDNA as a probe revealed that mouse FGF-1 is encoded by a single copy gene. Comparison of the available mouse Fgf-1 cDNA sequence with newly obtained genomic sequence allowed us to establish the exon/intron boundaries. The mouse Fgf-1 coding region is comprised of three protein coding exons, which we determined to be separated by an 11.4-kb and a 4.9-kb intron. The elucidation of the mouse Fgf-1 coding region revealed great similarity between the mouse and human Fgf-1 gene structure.
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PMID:Cloning and characterization of the mouse Fgf-1 gene. 897 5

Fibroblast growth factor 1 (FGF-1 or aFGF), is the prototype member of the heparin-binding growth factors which are capable of angiogenesis in vivo. FGF-1 has been implicated in atherosclerosis, cancer, wound repair and inflammatory autoimmune diseases. As part of an effort to understand the role of FGF-1 in the etiopathogenesis of inflammation and cancer, we have undertaken steps to isolate and characterize the mouse Fgf-1 gene. Southern blotting and sequence analysis displayed considerable conservation within the coding and upstream untranslated regions of Fgf-1 in human, mouse, hamster, rat and bovine. By using primers derived from the 5'-untranslated exon of a rat prostate-specific Fgf-1 cDNA, a 220-bp product was amplified from mouse genomic DNA via PCR. Sequence analysis of this amplicon showed that there was 80% similarity with the corresponding region of the rat FGF-cDNA sequence. Primers designed from this amplicon and the Fgf-1 coding region were used to isolate multiple overlapping genomic clones spanning the entire mouse Fgf-1 gene. Sequencing analysis of the genomic sequence upstream from this novel 5'-untranslated exon did not reveal typical TATA, CCAAT sequences. It appears that the occurrence of multiple untranslated exons for FGF-1 is a highly conserved theme for this gene across species.
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PMID:Cloning and characterization of a novel upstream untranslated exon of the mouse Fgf-1 gene. 897 57


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