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- Olofsson, P. S., et al.
(författare)
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Genetic variants of TNFSF4 and risk for carotid artery disease and stroke
- 2009
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Ingår i: Journal of Molecular Medicine. - New York : Springer. - 0946-2716 .- 1432-1440. ; 87:4, s. 337-346
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Tidskriftsartikel (refereegranskat)abstract
- In two independent human cohorts, the minor allele of SNP rs3850641 in TNFSF4 was significantly more frequent in individuals with myocardial infarction than in controls. In mice, Tnfsf4 expression is associated with increased atherosclerosis. The expression of TNFSF4 in human atherosclerosis and the association between genotype and cerebrovascular disease have not yet been investigated. TNFSF4 messenger RNA (mRNA) levels were significantly higher in human atherosclerotic lesions compared with controls (730∈±∈30 vs 330∈±∈65 arbitrary units, p∈<∈0.01). TNFSF4 was mainly expressed by macrophages in atherosclerotic lesions. In cell culture, endothelial cells upregulated TNFSF4 in response to tumor necrosis factor alpha (TNF-α; 460∈±∈110 vs 133∈±∈8 arbitrary units, p∈<∈0.001 after 6 h of stimulation). We analyzed the TNFSF4 gene in 239 patients who had undergone carotid endarterectomy and 138 matching controls from The Biobank of Karolinska Carotid Endarterectomies and Stockholm Heart Epidemiology Program cohorts and 929 patients and 1,382 matching controls from the Sahlgrenska Academy Study on Ischemic Stroke and Case Control Study of Stroke cohorts, limiting inclusion to patients with ischemic stroke. Participants were genotyped for the rs3850641 SNP in TNFSF4. Genotype associations were neither found with TNFSF4 mRNA levels nor with atherosclerosis associated systemic factors or risk for stroke. This study shows that TNFSF4 is expressed on antigen-presenting cells in human carotid atherosclerotic lesions but provides no evidence for an association of TNFSF4 gene variation with the risk for ischemic stroke.
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- Sultan, A., et al.
(författare)
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T cell-mediated inflammation in adipose tissue does not cause insulin resistance in hyperlipidemic mice
- 2009
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Ingår i: Circ Res. - 1524-4571 .- 0009-7330. ; 104:8, s. 961-8
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is associated with chronic inflammation in adipose tissue. Proinflammatory cytokines including tumor necrosis factor-alpha and interleukin-6 secreted by adipose tissue during the metabolic syndrome are proposed to cause local and general insulin resistance and promote development of type 2 diabetes. We have used a compound mutant mouse, Apoe(-/-)xCD4dnTGFbR, with dysregulation of T-cell activation, excessive production of proinflammatory cytokines, hyperlipidemia, and atherosclerosis, to dissect the role of inflammation in adipose tissue metabolism. These mice are lean, which avoids confounding effects of concomitant obesity. Expression and secretion of a set of proinflammatory factors including tumor necrosis factor-alpha, interferon-gamma, and monocyte chemoattractant protein-1 was increased in adipose tissue of Apoe(-/-)xCD4dnTGFbR mice, as was the enzyme 11beta-hydroxysteroid dehydrogenase type 1, which converts cortisone to bioactive cortisol. Interleukin-6, which has an inhibitory glucocorticoid response element in its promoter, was not upregulated. In spite of intense local inflammation, insulin sensitivity was not impaired in adipose tissue of Apoe(-/-)xCD4dnTGFbR mice unless exogenous interleukin-6 was administered. In conclusion, T-cell activation causes inflammation in adipose tissue but does not lead to insulin resistance in this tissue in the absence of interleukin-6.
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