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

Vascular endothelial cells derived from adult bovine aortic arch can be grown in two ways, either in the presence or absence of fibroblast growth factor. The types of collagen produced by cultures under these two conditions have been compared. In the presence of fibroblast growth factor, cells grow in an orderly fashion, express their normal phenotype and synthesize primarily type III collagen plus collagens types IV and V at a ratio of 10:1:3. Cultures grown in the absence of the factor lose their orderly pattern of growth, lose polarity and normal phenotypic expression. They devote twice the proportion of total protein-synthesizing capacity to collagen, and now synthesize type I in addition to the other collagen types. The ratio of collagen types I:III:IV:V is approximately 30:70:1:13. The kinds of type V collagen chains expressed are also altered. Fibroblast growth factor appears to modulate collagen synthesis, the major component of the extracellular matrix, and indirectly modulates the phenotypic expression of cultured vascular endothelial cells. In atherosclerosis, type I collagen is found in association with the intimal layer. The disorderly growth and the abnormal production of type I collagen by these vascular endothelial cells cultured in the absence of fibroblast growth factor is a model for a number of pathological situations including atherosclerotic plaque formation.
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PMID:Fibroblast growth factor modulates synthesis of collagen in cultured vascular endothelial cells. 646 Jun 22

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

Vascular smooth muscle cell (VSMC) proliferation associated with arterial injury causes restenosis, which remains to be resolved in cardiovascular and ischemic cerebrovascular disease, especially after balloon angioplasty. Fibroblast growth factor (FGF) is a potent mitogen and a trophic factor for a variety of cells, including VSMCs. We constructed a replication-deficient adenovirus vector, designated AxCA delta FR, coding a truncated form of fibroblast growth factor receptor-1 (FGFR-1) gene lacking the intracellular domain to interrupt receptor-mediated FGF signaling, and examined its effect on the proliferation of primary-cultured rat VSMCs. We transferred the truncated form of the FGFR-1 gene to the VSMCs and confirmed its expression and localization in infected cells by Western blotting and immunofluorescence study. The VSMCs infected with AxCA delta FR degenerated and the proliferation of these cells was suppressed markedly by the infection with this virus in vitro. Our results suggest that the receptor-mediated signal of FGFs has an important role in VSMC proliferation and gene transfer of a truncated form of FGFR using adenoviral vector may be useful for the treatment of the diseases caused by excessive proliferation of VSMCs like restenosis after percutaneous transluminal angioplasty or carotid endoarterectomy.
Atherosclerosis 1998 Nov
PMID:In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor. 986 45

Fibroblast growth factor 1 (FGF-1, also known as acidic FGF) 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 diseases. In the present study, the entire transcriptional unit of the mouse FGF-1 gene, including four promoters, is characterized. By nucleotide sequence and RNase protection analyses, we have determined that its 3'-end resides 3.2 kilobase pairs downstream from the stop codon. We have previously cloned and characterized the mouse homologue of the human 1B promoter, as well as a novel upstream untranslated exon. In order to elucidate the regulatory mechanism of FGF-1 gene expression, the mouse promoter containing TATA and CAAT consensus sequences (FGF-1. A) was isolated from a P1 library and characterized. We further determined that the mouse heart is the most abundant source for the FGF-1.A mRNA. Finally, via both RNase protection analysis and 5'-rapid amplification of cDNA ends, we determined the transcription start site of the FGF-1.A mRNA.
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PMID:Characterization of the entire transcription unit of the mouse fibroblast growth factor 1 (FGF-1) gene. Tissue-specific expression of the FGF-1.A mRNA. 1020 15

Endothelial dysfunction has been implicated in the pathogenesis of many cardiovascular diseases: experimental and clinical studies have shown that endothelial dysfunction may be a key factor in various processes, including abnormal arterial vasomotion, thrombosis or neointimial proliferation. Endothelial dysfunction has been shown to be a characteristic feature of atherosclerotic vessels, sites subject to mechanical injury or collateral vessels that develop in response to severe ischaemia. Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) are important growth factors for endothelial cells in vitro. While VEGF is specific for endothelial cells. FGFs are also potent growth factors for other cell types such as smooth muscle cells. Recent studies have demonstrated the feasibility of using endothelial cell growth factors in vivo. Basic FGF (bFGF) and VEGF have been shown to increase the development of collateral vessels in ischaemic models and to enhance the extent of endothelial regrowth following arterial injury. The marked anatomical improvement associated with the administration of endothelial cell growth factors has promoted questions concerning a possible role for these factors in endothelial dysfunction. In vivo administration of endothelial cell growth factors is associated with significant improvement in endothelium-dependent responses. This effect is observed with bFGF and VEGF in various animal models of endothelial dysfunction such as the collateral circulation, the regenerated endothelium following arterial injury and experimental atherosclerosis. While the precise mechanisms underlying this ubiquitous beneficial effect of endothelial cell growth factors are still to be determined, these results do support the concept of using such factors as a new therapeutic strategy in patients with vascular diseases.
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PMID:Growth factors and endothelial dysfunction. 1052 53

Endothelial dysfunction has been implicated in the pathogenesis of many cardiovascular diseases; experimental and clinical studies have shown that endothelial dysfunction may be a key factor in various processes, including abnormal arterial vasomotion, thrombosis or neointimal proliferation. Endothelial dysfunction has been shown to be a characteristic feature of atherosclerotic vessels, sites subject to mechanical injury or collateral vessels that develop in response to severe ischaemia. Fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) are important growth factors for endothelial cells in vitro. While VEGF is specific for endothelial cells, FGFs are also potent growth factors for other cell types such as smooth muscle cells. Recent studies have demonstrated the feasibility of using endothelial cell growth factors in vivo. Basic FGF (bFGF) and VEGF have been shown to increase the development of collateral vessels in ischaemic models and to enhance the extent of endothelial regrowth following arterial injury. The marked anatomical improvement associated with the administration of endothelial cell growth factors has promoted questions concerning a possible role for these factors in endothelial dysfunction. In vivo administration of endothelial cell growth factors is associated with significant improvement in endothelium-dependent responses. This effect is observed with bFGF and VEGF in various animal models of endothelial dysfunction such as the collateral circulation, the regenerated endothelium following arterial injury and experimental atherosclerosis. While the precise mechanisms underlying this ubiquitous beneficial effect of endothelial cell growth factors are still to be determined, these results do support the concept of using such factors as a new therapeutic strategy in patients with vascular diseases.
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PMID:Growth factors and endothelial dysfunction. 1054 87

Fibroblast growth factor-2 (FGF-2) is a member of a large family of proteins that bind heparin and heparan sulfate and modulate the function of a wide range of cell types. FGF-2 stimulates the growth and development of new blood vessels (angiogenesis) that contribute to the pathogenesis of several diseases (i.e. cancer, atherosclerosis), normal wound healing and tissue development. FGF-2 contains a number of basic residues (pI 9.6) and consists of 12 anti-parallel beta-sheets organized into a trigonal pyrimidal structure. FGF-2 binds to four cell surface receptors expressed as a number of splice variants. Many of the biological activities of FGF-2 have been found to depend on its receptor's intrinsic tyrosine kinase activity and second messengers such as the mitogen activated protein kinases. However, considerable evidence suggest that intracellular FGF-2 might have a direct biological role particularly within the nucleus. In addition, heparan sulfate proteoglycans have been demonstrated to enhance and inhibit FGF-2 activity. The possibility that FGF-2 activity can be manipulated through alterations in heparan sulfate-binding is currently being exploited in the development of clinical applications aimed at modulating either endogenous or administered FGF-2 activity.
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PMID:Fibroblast growth factor-2. 1068 47

White carneau (WC) pigeons develop spontaneous atherosclerosis in contrast to atherosclerosis-resistant show racer (SR) pigeons. In this study, cellular and extracellular components and smooth muscle cell (SMC) proliferation rates of specific aortic sites were assessed in both breeds of pigeons prior to lesion development. The atherosclerosis-susceptible site of the WC aorta was characterized by larger lumen diameter without accompanying increase in wall thickness, as well as by SMC hypocellularity, increased proteoglycan content and higher elastin content. For both breeds, cells derived from the lesion site had lower proliferation rates compared to proximal aortic control sites. WC cells had greater proliferation rates than SR cells (109% greater at the atherosclerosis-prone site and 133% greater at the control site). Fibroblast growth factor (FGF) increased the proliferation of WC lesion site cells compared to SR cells (79% vs. 35%); whereas, transforming growth factor beta (TGFbeta) reduced growth in SR but not in WC cells. Differences in hemodynamic properties, in cell-matrix, elastin, proteoglycan and proliferation rates of cells and responses to FGF and TGFbeta in cells of the atherosclerosis-prone area have been identified as potential contributors to the enhanced atherosclerosis potential of this site in WC pigeons.
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PMID:Artery regional properties and atherosclerosis susceptibility. 1708 16

Fibroblast growth factor 2 (FGF2) consists of multiple protein isoforms (low molecular weight, LMW, and high molecular weight, HMW) produced by alternative translation from the Fgf2 gene. These protein isoforms are localized to different cellular compartments, indicating unique biological activity. FGF2 isoforms in the heart have distinct roles in many pathological circumstances in the heart including cardiac hypertrophy, ischemia-reperfusion injury, and atherosclerosis. These studies suggest distinct biological activities of FGF2 LMW and HMW isoforms both in vitro and in vivo. Yet, due to the limitations that only the recombinant FGF2 LMW isoform is readily available and that the FGF2 antibody is nonspecific with regards to its isoforms, much remains to be determined regarding the role(s) of the FGF2 LMW and HMW isoforms in cellular behavior and in cardiovascular development and pathophysiology. This review summarizes the activities of LMW and HMW isoforms of FGF2 in cardiovascular development and disease.
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PMID:Biological functions of the low and high molecular weight protein isoforms of fibroblast growth factor-2 in cardiovascular development and disease. 1877 89


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