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)

1. Endothelial dysfunction and vascular smooth muscle cell (VSMC) proliferation are key events in the pathogenesis of atherosclerosis. Vascular permeability factor (VPF), an endothelial-cell-specific multifunctional cytokine, was recently described, and has the potential to contribute to the development of endothelial dysfunction. The present study determines whether cultured human VSMCs express mRNA for VPF and whether VPF mRNA expression is influenced by human VSMC proliferation. 2. A 204 bp cDNA fragment, specific for all known variants of VPF mRNA, was cloned and used to demonstrate that human VSMCs express abundant quantities of VPF mRNA, whereas human endothelial cells do not. VPF mRNA levels were markedly diminished in non-proliferating human VSMCs. In contrast, when human VSMCs were stimulated to proliferate by exposure to serum, there was a rapid 6.6-fold increase (P < 0.01 versus time 0 h) in VPF mRNA expression, which was maximal at 3 h and persisted beyond 24 h. The magnitude of the VPF mRNA response in human VSMCs was dependent on the serum concentration. 3. Platelet-derived growth factor also increased VPF mRNA expression by human VSMCs, thus confirming that recognized growth factors for VSMCs also potently influence the VPF gene. 4. In conclusion, VPF mRNA is expressed by human VSMCs, the magnitude of VPF expression being temporally related to the proliferation of human VSMCs and the potency of the growth-promoting stimulus. We propose that VPF produced by proliferating human VSMCs could act as a paracrine hormone to powerfully influence the permeability and growth of the overlying vascular endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum and platelet-derived growth factor-induced expression of vascular permeability factor mRNA by human vascular smooth muscle cells in vitro. 772 Mar 37

Angiotensin II (Ang II) has been implicated in the pathogenesis of the vascular injury associated with hypertension and diabetes mellitus. Increased vascular permeability is an important early manifestation of endothelial dysfunction and the pathogenesis of atherosclerosis. How Ang II contributes to endothelial dysfunction and promotes an increase in vascular permeability is unknown but is classically attributed to its pressor actions. We demonstrate that human vascular smooth muscle cells express abundant mRNA for vascular permeability/endothelial growth factor. Vascular permeability factor is a 34- to 42-kD glycoprotein that markedly increases vascular endothelial permeability and is a potent endothelial mitogen. Ang II potently induced a concentration-dependent (maximal, 10(-7) mol/L) and time-dependent increase in vascular permeability factor mRNA expression by human vascular smooth muscle cells that was maximal after 3 hours and diminished by 24 hours. Ang II-induced vascular permeability factor mRNA expression by human vascular smooth muscle cells was inhibited by the specific Ang II receptor antagonist losartan (DuP 753), confirming that this is an Ang II receptor subtype 1-mediated event. These results describe a new action of Ang II on human vascular smooth muscle, notably the induction of vascular permeability factor mRNA expression. The wide spectrum and potent activity of vascular permeability factor suggest a novel mechanism whereby Ang II could locally and directly influence the permeability, growth, and function of the vascular endothelium independent of changes in hemodynamics.
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PMID:Angiotensin II increases vascular permeability factor gene expression by human vascular smooth muscle cells. 773 26

Vascular endothelial growth factor (VEGF) mRNA expression was analysed in rabbit vascular smooth muscle cells following exposure to hypoxia and platelet-derived growth factor-BB (PDGF-BB). Hypoxia potently upregulated VEGF mRNA steady-state levels in a time- and concentration-dependent manner reaching a maximum level (approximately 30-fold increase) after 12-24 h at 0% 0(2). In contrast, PDGF-BB caused a modest increase in VEGF expression. However, the combination of PDGF-BB and a threshold hypoxic stimulus (2.5% O2 for 4 h) had a marked synergistic effect. Synergy between hypoxia and PDGF-BB was selective for VEGF expression as hypoxia had no effect on the PDGF-induced upregulation of the proto-oncogene c-myc. These results raise the possibility that hypoxia and PDGF-BB may act in concert to induce VEGF expression in the arterial wall during the development of atherosclerosis.
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PMID:Hypoxia and platelet-derived growth factor-BB synergistically upregulate the expression of vascular endothelial growth factor in vascular smooth muscle cells. 784 20

Angiogenesis, the sprouting of new blood vessels from pre-existing vessels, is a complex, multicellular phenomenon involving capillary endothelial cell (EC) proliferation, migration, and tissue infiltration. The elucidation of the biochemical and molecular factors which control angiogenesis is fundamental to our understanding of normal blood vessel development, as well as of the pathogenesis of abnormal blood vessel formation. Angiogenesis is associated with numerous physiological processes, including embryogenesis, wound healing, organ regeneration, and the female reproductive cycle. However, abnormal angiogenesis also plays a major role in the pathogenesis of tumor growth, rheumatoid arthritis, atherosclerosis and various retinopathies. The cellular and molecular mechanisms underlying both physiological and pathophysiological angiogenesis are only now beginning to be understood. Vascular endothelial growth factor was initially discovered as an unidentified tumor-derived factor which increased microvascular permeability (vascular permeability factor, VPF). Subsequently, it was determined that the protein exhibited mitogenic effects on endothelial cells, but not other cell types. Multiple receptor subtypes have been described which may in part explain the multiplicity of biological actions that have been ascribed to VEGF/VPF in the literature. In this overview, we briefly summarize what is currently known about VEGF and VEGF receptor biology, as well as VEGF receptor signal transduction mechanisms in endothelial cells.
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PMID:Vascular endothelial growth factor, a multifunctional polypeptide. 899 81

Vascular endothelial growth factor (VEGF), in addition oto its growth-promoting effects on endothelial cells, can also increase vascular permeability and monocyte migration. It has therefore been implicated in the pathogenic neovascularization associated with diabetic retinopathy and atherosclerosis. However, the factors regulating VEGF expression in the vascular wall are not fully understood. In this study, we examined the regulation of VEGF expression in vascular smooth muscle cells (VSMC) by hyperglycemia as well as by angiotensin II (ANG II). We also examined whether the 12-lipoxygenase (12-LO) product 12-hydroxyeicosatetraenoic acid (12-HETE) can alter VEGF expression, since 12-LO products of arachidonic acid have angiogenic properties, and ANG II as well as high glucose (HG, 25 mM) can increase 12-LO activity and expression in VSMC. Studies were carried out in human (HSMC) or porcine VSMC (PSMC), which were cultured for at least two passages under normal glucose (NG, 5.5 mM) or HG conditions. HG culture alone increased the expression of VEGF mRNA and protein in both HSMC and PSMC. Furthermore, ANG II treatment significantly induced VEGF mRNA and protein expression only in VSMC cultured in HG and not NG. In addition, 12-HETE significantly increased VEGF mRNA and protein expression in HSMC cultured in NG as well as in HG. Cells cultured in HG also secreted significantly greater amounts of VEGF into the culture medium. These results suggest that elevated VEGF production under HG conditions may play a role in the accelerated vascular disease observed in diabetes.
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PMID:Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells. 937 57

Vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a specific mitogen for vascular endothelial cells and causes neovascularization and capillary hyperpermeability. We previously found large amounts of VEGF peptide in areas with many macrophage-derived foam cells adjacent to the lipid core of human atherosclerotic plaques and in basal regions of plaque consisting predominantly of smooth muscle cells. In the present study, we examined the role of inflammatory cytokines and oxidative modified low density lipoprotein (OX-LDL) in the expression of macrophage VEGF. Interleukin 1 beta and tumor necrosis factor alpha upregulated the expression of VEGF mRNA in a macrophage cell line (RAW264). In addition, OX-LDL also upregulated the expression of VEGF mRNA in these cells in a time-dependent and a dose-dependent dependent manner, and there was an increase in the levels of VEGF protein in the conditioned medium. These results suggest that VEGF expression may be upregulated in atherosclerotic lesions and that VEGF may play a role in the development of atherosclerosis.
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PMID:[Effect of inflammatory cytokines and oxidized low density lipoprotein on vascular endothelial growth factor expression in macrophage]. 964 7

The interaction between macrophages and oxidatively modified low density lipoprotein (Ox-LDL) appears to play a central role in the development of atherosclerosis, not only through foam cell formation but also via the induction of numerous cytokines and growth factors. The current study demonstrated that Ox-LDL upregulated vascular endothelial growth factor (VEGF) mRNA expression in RAW 264 cells, a monocytic cell line, in a time- and concentration-dependent manner and that Ox-LDL stimulated VEGF protein secretion from the cells. Lysophosphatidylcholine, a component of Ox-LDL, also enhanced VEGF mRNA expression in RAW 264 cells and VEGF secretion from RAW 264 cells, with a maximal effect at a concentration of 10 micromol/L lysophosphatidylcholine. Immunohistochemical studies showed that human early atherosclerotic lesions exhibited intense VEGF immunoreactivity in subendothelial macrophage-rich regions of the thickened intima. In atherosclerotic plaques, VEGF staining was also observed in foam cell-rich regions adjacent to the lipid core or the neovascularized basal regions of plaque consisting predominantly of smooth muscle cells. High-power-field observation revealed that VEGF was localized in the extracellular space as well as at the macrophage cell surface. These observations suggest the possible involvement of Ox-LDL in the development of human atherosclerosis through VEGF induction in macrophages.
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PMID:Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions. 967 81

The precise regulation of cell growth in the vascular wall maintains vascular integrity, and its disruption leads to cardiovascular disorders including atherosclerosis and restenosis. Vascular endothelial growth factor (VEGF) is a specific mitogen for endothelial cells, and endothelin-1 (ET-1) is known to stimulate the proliferation of smooth muscle cells. The aim of this study was to explore a potential interaction between VEGF and ET-1 on each expression in vascular cells. VEGF enhanced preproET-1 mRNA expression and ET-1 secretion in bovine aortic endothelial cells (BAECs). Similarly, in rat vascular smooth muscle cells (VSMCs), ET-1 enhanced VEGF mRNA expression and stimulated VEGF secretion. ET-1-induced VEGF mRNA expression was abolished by a selective ET(A) receptor antagonist, BQ-485, but not by an ET(B)-selective blocker, BQ-788. It was also inhibited by pretreatment with actinomycin D but not by pretreatment with cycloheximide. Furthermore, the actinomycin D chase experiment revealed that ET-1 did not alter VEGF mRNA stability. Coculture of BAECs and VSMCs enhanced both ET-1 and VEGF gene expression in these cells, and the conditioned media from BAECs and VSMCs reproduced the augmentation of each gene expression, which was partially inhibited by BQ-485 or an antibody specific to VEGF. Our results indicate that VEGF and ET-1 have stimulatory interactions on each expression, which may play an important role in concomitant proliferation of endothelial and smooth muscle cells in the vascular wall.
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PMID:Stimulatory interaction between vascular endothelial growth factor and endothelin-1 on each gene expression. 967 43

VEGF-C is a recently characterised endothelial growth factor structurally related to vascular endothelial growth factor (VEGF). We studied the expression of VEGF-C and VEGF in the cells of peripheral blood and in the umbilical cord blood CD 34+ cells, representing haematopoietic progenitor cells. Expression of VEGF-C was detected in the CD34+ cells. In peripheral blood VEGF-C mRNA was restricted to platelets and T-cells. In contrast to the expression pattern of VEGF-C, VEGF mRNA was detected in all peripheral blood cell fractions studied, and also in CD34+ cells. VEGF-C mRNA was also detected in fresh bone marrow samples of acute leukaemia patients, but the expression did not show lineage specificity. VEGF-C and VEGF polypeptides were present in platelets and they were released from activated platelets together with the release of beta-thromboglobulin, suggesting that VEGF-C and VEGF reside in the alpha-granules of platelets. VEGF-C and VEGF, released from activated platelets, may have a role in angiogenesis during wound healing, and possibly also in other pathological conditions, such as atherosclerosis, tumour growth, and metastasis formation.
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PMID:Peripheral blood platelets express VEGF-C and VEGF which are released during platelet activation. 968 5

The objective of this study was to investigate whether synthesis of vascular endothelial growth factor (VEGF), a major mitogen for vascular endothelial cells, was induced by a cell-to-cell interaction between monocytes and vascular smooth muscle cells (VSMCs). Human VSMCs and THP-1 cells (human monocytoid cell) were cocultured. VEGF levels in the coculture medium were determined by enzyme-linked immunosorbent assay. Northern blot analysis of VEGF mRNA was performed using a specific cDNA probe. Immunohistochemistry was performed to determine which types of cell produce VEGF. Adding THP-1 cells to VSMCs for 24 h increased VEGF levels of the culture media, 8- and 10-fold relative to those of THP-1 cells and VSMCs alone, respectively. Northern blot analysis showed that VEGF mRNA expression was induced in the cocultured cells and peaked after 12 h. Immunohistochemistry disclosed that both types of cell in the coculture produced VEGF. Separate coculture experiments revealed that both direct contact and a soluble factor(s) contributed to VEGF production. Neutralizing anti-interleukin (IL)-6 antibody inhibited VEGF production by the coculture of THP-1 cells and VSMCs. A cell-to-cell interaction between monocytes and VSMCs induced VEGF synthesis in both types of cell. An IL-6 mediated mechanism is at least partially involved in VEGF production by the cocultures. Local VEGF production induced by a monocyte-VSMC interaction may play an important role in atherosclerosis and vascular remodeling.
Atherosclerosis 2000 May
PMID:Interaction between human monocytes and vascular smooth muscle cells induces vascular endothelial growth factor expression. 1078 36


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