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- Zandi, Peter P, et al.
(författare)
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Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.
- 2004
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Ingår i: Archives of neurology. - : American Medical Association (AMA). - 0003-9942. ; 61:1, s. 82-8
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD). OBJECTIVE: To examine the relationship between antioxidant supplement use and risk of AD. DESIGN: Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact. SETTING: Cache County, Utah. PARTICIPANTS: Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up. MAIN OUTCOME MEASURE: Diagnosis of AD by means of multistage assessment procedures. RESULTS: Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements. CONCLUSIONS: Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD.
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- Dixelius, J, et al.
(författare)
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Laminin-1 promotes angiogenesis in synergy with fibroblast growth factor by distinct regulation of the gene and protein expression profile in endothelial cells
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 279:22, s. 23766-23772
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Tidskriftsartikel (refereegranskat)abstract
- Laminins are widely distributed extracellular matrix proteins. Certain laminin isoforms are predominant in vascular basement membranes and may be critical in maintaining the stability of the mature vessel. On the other hand, formation of new vessels during angiogenesis requires degradation of the basement membrane, exposing the endothelial cells to other laminin isoforms in the surrounding extracellular matrix. We studied the effects of laminin-1 (LN-1) in different in vitro and in vivo models for angiogenesis. LN-1 induced angiogenesis in the chicken chorioallantoic membrane to the same extent as fibroblast growth factor-2 (FGF-2), and vascular development in embryoid bodies was stimulated in a synergistic manner by FGF-2 and LN-1. LN-1 promoted differentiation of endothelial cells in three-dimensional collagen gels, both in the absence and presence of FGF-2. Formation of tubular structures induced by LN-1 was accompanied by increased expression of Jagged-1, a marker of endothelial differentiation, and increased levels of FGF-2 and FGFR-1 transcripts. LN-1 did not regulate signal transduction pathways known to operate down stream of FGF-2. Thus, phosphorylation of ERK was detected in FGF-2- but not in LN-1-treated cells. Taken together, this suggests that laminins may play a fundamental role in angiogenesis by directly affecting gene and protein expression profiles in endothelial cells.
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- Lundin, Lars, et al.
(författare)
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Selectively desulfated heparin inhibits fibroblast growth factor-induced mitogenicity and angiogenesis.
- 2000
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 275:32, s. 24653-24660
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Tidskriftsartikel (refereegranskat)abstract
- Fibroblast growth factors (FGFs) are known to induce formation of new blood vessels, angiogenesis. We show that FGF-induced angiogenesis can be modulated using selectively desulfated heparin. Chinese hamster ovary cells (CHO677) deficient in heparan sulfate biosynthesis were employed to assess the function of heparin/heparan sulfate in FGF receptor-1 (FGFR-1) signal transduction and biological responses. In the presence of FGF-2, FGFR-1 kinase and subsequent mitogen-activated protein kinase Erk2 activities were augmented in a dose-dependent manner, whereas high concentrations of heparin resulted in decreased activity. The length of the heparin oligomer, minimally an 8/10-mer, was critical for the ability to enhance FGFR-1 kinase activity. The N- and 2-O-sulfate groups of heparin were essential for binding to FGF-2, whereas stimulation of FGFR-1 and Erk2 kinases by FGF-2 also required the presence of 6-O-sulfate groups. Sulfation at 2-O- and 6-O-positions was moreover a prerequisite for binding of heparin to a lysine-rich peptide corresponding to amino acids 160-177 in the extracellular domain of FGFR-1. Selectively 6-O-desulfated heparin, which binds to FGF-2 but fails to bind the receptor, decreased FGF-2-induced proliferation of CHO677 cells, presumably by displacing intact heparin. Furthermore, FGF-2-induced angiogenesis in chick embryos was inhibited by 6-O-desulfated heparin. Thus, formation of a ternary complex of FGF-2, heparin, and FGFR-1 appears critical for the activation of FGFR-1 kinase and downstream signal transduction. Preventing complex formation by modified heparin preparations may allow regulation of FGF-2 functions, such as induction of angiogenesis.
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