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)

This review provides a scientific assessment of current knowledge of health effects of soybean oil (SBO) and sunflower oil (SFO). SBO and SFO both contain high levels of polyunsaturated fatty acids (PUFA) (60.8 and 69%, respectively), with a PUFA:saturated fat ratio of 4.0 for SBO and 6.4 for SFO. SFO contains 69% C18:2n-6 and less than 0.1% C18:3n-3, while SBO contains 54% C18:2n-6 and 7.2% C18:3n-3. Thus, SFO and SBO each provide adequate amounts of C18:2n-6, but of the two, SBO provides C18:3n-3 with a C18:2n-6:C18:3n-3 ratio of 7.1. Epidemiological evidence has suggested an inverse relationship between the consumption of diets high in vegetable fat and blood pressure, although clinical findings have been inconclusive. Recent dietary guidelines suggest the desirability of decreasing consumption of total and saturated fat and cholesterol, an objective that can be achieved by substituting such oils as SFO and SBO for animal fats. Such changes have consistently resulted in decreased total and low-density-lipoprotein cholesterol, which is thought to be favorable with respect to decreasing risk of cardiovascular disease. Also, decreases in high-density-lipoprotein cholesterol have raised some concern. Use of vegetable oils such as SFO and SBO increases C18:2n-6, decreases C20:4n-6, and slightly elevated C20:5n-3 and C22:6n-3 in platelets, changes that slightly inhibit platelet generation of thromboxane and ex vivo aggregation. Whether chronic use of these oils will effectively block thrombosis at sites of vascular injury, inhibit pathologic platelet vascular interactions associated with atherosclerosis, or reduce the incidence of acute vascular occlusion in the coronary or cerebral circulation is uncertain. Linoleic acid is needed for normal immune response, and essential fatty acid (EFA) deficiency impairs B and T cell-mediated responses. SBO and SFO can provide adequate linoleic acid for maintenance of the immune response. Excess linoleic acid has supported tumor growth in animals, an effect not verified by data from diverse human studies of risk, incidence, or progression of cancers of the breast and colon. Areas yet to be investigated include the differential effects of n-6- and n-3-containing oil on tumor development in humans and whether shorter-chain n-3 PUFA of plant origin such as found in SBO will modulate these actions of linoleic acid, as has been shown for the longer-chain n-3 PUFA of marine oils.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Food use and health effects of soybean and sunflower oils. 195 19

A new approach to study the distribution of fibrin(ogen)-related antigens was investigated using three different monoclonal antibodies (MAbs) and the avidin-biotin complex immunoperoxidase technique. MAb I8C6 recognizes B beta 1-42 peptide and can react with either fibrinogen or fibrin I; MAb T2G1 recognizes B beta 15-42 peptide and detects fibrin II but does not cross-react with fibrinogen; MAb GC4 reacts with Fragments D/DD derived from plasmin degradation of fibrinogen or fibrin but not with intact fibrinogen. The method can be applied to frozen or Bouin's fixed paraffin-embedded tissues obtained at biopsy, surgery, and autopsy. The distribution of the three antigens observed with the three MAbs was compared with that obtained with a polyclonal antiserum to fibrinogen and with the more conventional histochemical stains used in pathology to demonstrate fibrin deposits in tissues (Lendrum and PTAH). The staining observed with the three monoclonals clearly detected three different populations of fibrin(ogen)-related antigen in the tissues examined. The staining with MAb T2G1 specifically detected fibrin II with greater sensitivity than did conventional stains. The results of this study suggest that this method allows the molecular form of fibrin(ogen)-related deposits in tissues to be determined and this information may help to elucidate the role of fibrin in various disease states, such as atherosclerosis and renal disease, and in tumor growth and metastasis.
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PMID:Immunohistochemical characterization of fibrin(ogen)-related antigens in human tissues using monoclonal antibodies. 265 90

The successful evaluation of tamoxifen as an antiestrogenic therapy for advanced breast cancer in the early 1970's, has resulted in its availability in more than 70 countries around the world. Currently the drug development process is focusing attention upon long-term adjuvant therapy and the future prospect of chemosuppression. Progress at this stage, however, must be cautious. Trials conducted using women with stage I disease have a high proportion of women who may never have a recurrence. At this point, the risk is justified because the toxicity of tamoxifen is low and disease recurrence is invariably very difficult or impossible to control. Future studies in the general population must be carefully weighed to ensure that the hazards do not exceed the benefits. The pharmacology of tamoxifen seems to be a balance of estrogenic and antiestrogenic effects. Longer treatments with the drug must be carefully monitored. Uterine tissue should be examined to ensure that excessive stimulation does not occur. This is particularly true in the light of the recent report that a human uterine carcinoma, transplanted into athymic mice, can grow more rapidly during tamoxifen therapy (Satyaswaroop et al., 1984; Clark and Satyaswaroop, 1985). In fact, we have recently confirmed this observation in a collaborative study with Dr. Satyaswaroop. We have demonstrated that when athymic mice are transplanted in one axilla with an MCF-7 breast tumor and the human endometrial tumor in the other, tamoxifen causes the endometrial tumor to grow, but not the breast tumor. This again illustrates the target site specific effects of tamoxifen. If, in the long run, the estrogenic side effects of tamoxifen are too severe then there is a case for the development of a non-estrogenic antiestrogen. Clearly this may provide benefit for short term (1-2 years) therapy and avoid any estrogen-like stimulation of tumor growth. Similarly, the concern about antithrombin III depression will be avoided. On the negative side, however, the concerns about atherosclerosis and osteoporosis will again have to be addressed with a new generation of agents.
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PMID:Long-term tamoxifen therapy to control or to prevent breast cancer: laboratory concept to clinical trials. 328 87

T lymphocytes infiltrate wounds, tumors, and atherosclerotic plaques, pathophysiological processes characterized by the migration and proliferation of vascular cells and fibroblasts. Although T lymphocytes are known to produce cytokines for inflammatory cells, it has not been demonstrated that they synthesize growth factors that are mitogenic for vascular cells and fibroblasts. We demonstrate that cultured T lymphocytes isolated from normal human peripheral blood synthesize and export two well-characterized growth factors, heparin-binding epidermal growth factor-like growth factor (HB-EGF) and basic fibroblast growth factor (bFGF). This conclusion is based on mRNA expression analysis, heparin-affinity chromatography profiles, target-cell specificity, and functional inhibition by specific neutralizing antibodies. Atypically, a substantial amount of T-cell-derived bFGF-like activity appears to be constitutively released into conditioned medium, almost as much as is associated with T-cell lysates. bFGF is synthesized and exported by purified CD4+ and CD8+ T cells, whereas HB-EGF is synthesized and exported primarily by CD4+ T cells. The T-cell-derived HB-EGF and bFGF activities are potent mitogens for fibroblasts and smooth muscle cells, and the bFGF-like activity is also mitogenic for endothelial cells. These results suggest that T lymphocytes may play key roles in mediating smooth muscle hyperplasia associated with atherosclerosis and in angiogenesis associated with wound healing and tumor growth by acting locally to deliver vascular-cell growth factors to tissues.
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PMID:T lymphocytes synthesize and export heparin-binding epidermal growth factor-like growth factor and basic fibroblast growth factor, mitogens for vascular cells and fibroblasts: differential production and release by CD4+ and CD8+ T cells. 815 70

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

HB-EGF is a heparin-binding member of the EGF family that was initially identified in the conditioned medium of human macrophages. Soluble mature HB-EGF is proteolytically processed from a larger membrane-anchored precursor and is a potent mitogen and chemotactic factor for fibroblasts, smooth muscle cells but not endothelial cells. HB-EGF activates two EGF receptor subtypes, HER1 and HER4 and binds to cell surface HSPG. The transmembrane form of HB-EGF is a juxtacrine growth and adhesion factor and is uniquely the receptor for diphtheria toxin. HB-EGF gene expression is highly regulated, for example by cytokines, growth factors, and transcription factors such as MyoD. HB-EGF has been implicated as a participant in a variety of normal physiological processes such as blastocyst implantation and wound healing, and in pathological processes such as tumor growth, SMC hyperplasia and atherosclerosis.
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PMID:Heparin-binding EGF-like growth factor. 942 3

This workshop intended to perform a "state-of-the art" of current research on adhesion molecules in various pathophysiologies, and to determine pharmacological targets. Indeed, recent important progress concerning the cellular and molecular physiology of adhesion molecules led to the development of various integrin antagonists in several domains, like cardiovascular disease, inflammation and cancer. Integrins play a major role in numerous process like embryonic development, tumor growth and metastasis, apoptosis, hemostasis, leucocyte recruitment and activation, and bone resorption. The development of integrin antagonists is well advanced in the cardiovascular domain, since the first marketed drug (abciximax, Reopro) is an antibody directed against the GPIIb/IIIa complex (integrin alpha IIb/beta 3) involved in the final pathway of platelet aggregation. Another active domain of research in pharmacology is 'cardioprotection', i.e. the prevention of cardiac damages induced by the reperfusion of the coronary bed after an ischemia secondary to thrombolysis, angioplasty, of coronary bypass. The pharmacological targets of these antagonists are integrins involved in various process like leucocyte and platelet adhesion and endothelial function. Other potential indications in the cardiovascular field are restenosis after angioplasty, and atherosclerosis.
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PMID:[Cell adhesion molecules and pharmacologic applications. Round Table No 3 at Giens XIII]. 980 7

Oxidative stress and free radical-mediated cell death have been linked to diseases such as atherosclerosis, Alzheimer's disease, and cancer. Estrogens may promote, or offer protection against these conditions, by acting both as an antioxidant and prooxidant. Estrogens are converted to catecholestrogens via an oxidation step. Catecholestrogens are precursors of quinones that undergo a reversible oxidation-reduction reaction yielding semiquinones and reactive oxygen species. These semiquinones and reactive oxygen species may act as prooxidants and result in DNA and protein damage that may play a role in initiating tumor growth. Estrogen may also stimulate the peroxidase reaction, thereby promoting prooxidant reactions catalyzed by estrogen. Such reactions may be involved in enhancing the oxidizability of low-density lipoproteins (LDL). This mechanism of oxidation of LDL in plasma may actually lead to increased clearance of LDL by the liver and thereby contribute to estrogens' antiatherogenic action. On the other hand, participation of catecholestrogens in iron redox cycling may contribute to the antioxidant action of estrogens. This action might be important in sites such as the subendothelial space where estrogens are thought to inhibit LDL oxidation. Estrogens may also exert antioxidant effects by acting on genes with response elements for antioxidants. This may in turn inhibit expression of certain proteins involved in disease processes such as atherogenesis. Thus, by acting as an antioxidant and prooxidant, estrogen may produce both beneficial and adverse effects important in the prevention and pathogenesis of disease.
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PMID:Antioxidant and prooxidant actions of estrogens: potential physiological and clinical implications. 1010 11

Neovascularization of the atherosclerotic plaque is responsible for its weakening and consequently for the complications of vascular disease. Macrophages are a source of growth factors that can modulate angiogenesis. In this study, we analyzed the effect of oncostatin M (OSM) on angiogenesis, as it could be involved in the development of atherosclerosis. The effect of OSM was compared with those of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). On human dermal microvasculature endothelial cells (HMEC-1s), OSM (22.5 to 112.5 pmol/L) induced a dose-dependent increase in cell proliferation greater than that induced by the classic angiogenic factors vascular endothelial growth factor (VEGF; 543 pmol/L) and basic fibroblast growth factor (bFGF; 1.1 nmol/L). LIF (19 to 475 pmol/L) induced only a 30% increase in cell proliferation, and IL-6 had no effect. Furthermore, in a modified Boyden-chamber model, OSM, LIF, and IL-6 were chemoattractant for HMEC-1s. In a tridimensional gel of fibrin, OSM increased tube formation and tube length, which were already noticeable by day 3. LIF and IL-6 induced a weaker effect that was only obvious by day 10. The angiogenic effect of OSM was also demonstrated in vivo in a rabbit corneal model: OSM was more potent than LIF, the length of the neovessels being longer with OSM than with LIF, whereas IL-6 was without effect. We tested factors that could be involved in the proliferative effect of OSM on HMEC-1s. OSM induced only a slight increase in the urokinase receptor and a 60% increase in VEGF secretion, whereas it does not modify IL-8 secretion or bFGF levels. The effect of OSM seems to depend on endothelial cell origin and cell species: OSM (up to 112.5 pmol/L) did not induce human umbilical vein endothelial cell proliferation and even had a small inhibitory effect (17%) on calf pulmonary artery endothelial cells. In conclusion, OSM induces an angiogenic effect on capillary endothelial cells, which could be, at least in part, implicated in pathological processes such as atherosclerosis or tumor growth.
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PMID:Oncostatin M induces angiogenesis in vitro and in vivo. 1044 61

Green tea, the most popular beverage in Japan and China, contains epicatechin-derived compounds which have been characterized in some epidemiological studies as having protective effects against cancer. Epigallo catechin-O-gallate (EGCG), the most active epicatechin in green tea was previously found to block the in vitro growth of many cancer cell lines and in vivo to strongly reduce tumor growth in cancer-bearing animals. Today, green tea consumption by animals is shown to markedly reduce VEGF-induced angiogenesis, a neo-vascularization process occurring in several physio-pathological conditions. EGCG is also able to inhibit endothelial cell growth in vitro and angiogenesis process in vivo. Elsewhere, EGCG has been described as a potent inducer of apoptosis and an inhibitor of telomerase activity. Because EGCG is acting on different processes, it could trigger various molecular mechanisms of action. Its anti-oxidant properties could explain its antagonistic action in some inflammatory processes. In summary, although no direct molecular target has been so far elucidated for EGCG, the multi-potentialities of this molecule, along with its broad bioavailability, render it very attractive as a putative curative drug for various diseases such as dermatosis, gout, atherosclerosis and cancer.
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PMID:[Multiple actions of EGCG, the main component of green tea]. 1051 63


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